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Coniine forms with carbon disulphide a thiosulphate and a sulphite. If carbon disulphide, therefore, be shaken with an aqueous solution of coniine, the watery solution gives a brown precipitate with copper sulphate, colours ferric chloride solution dark brown red, and gives a milky opalescence with dilute acids. If coniine itself is added to carbon disulphide, there is evolution of heat, separation of sulphur, and formation of thiosulphate. Nicotine does not respond to this reaction.

§ 320. Other Coniine Bases.—Methyl- and ethyl-coniine have been prepared synthetically, and are both similar in action to coniine, but somewhat more like curarine. By the reduction of coniine with zinc dust conyrine (C₈H₁₁N) is formed; between coniine and conyrine stands coniceine (C₈H₁₅NO). De Coninck has made synthetically by the addition of 6 atoms of hydrogen to β collidine, a new fluid alkaloid (C₈H₁₁N + 6H = C₈H₁₇N), which he has called isocicutine: it has the same formula as coniine. Paraconiine Schiff prepared synthetically from ammonia and normal butyl aldehyde; it has the formula C₈H₁₅N, and therefore differs from coniine in containing two atoms less of hydrogen. All the above have a similar physiological action to coniine. α-stillbazoline (C₁₁H₁₉N), prepared by Baurath from benzaldehyde and picoline, is analogous to coniine, and according to Falck has similar action, but is more powerful.

§ 321. Pharmaceutical Preparations.—The percentage of coniine in the plant itself, and in pharmaceutical preparations, can be approximately determined by distilling the coniine over, in a partial vacuum,[344] and titrating the distillate with Mayer’s reagent, each c.c. = about ·00416 grm. of coniine. It appears to be necessary to add powdered potassic chloride and a small quantity of diluted sulphuric acid before titrating, or the precipitate does not separate. In any case, the end of the reaction is difficult to observe.[345]

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The fresh plant is said to contain from about ·04 to ·09 per cent., and the fruit about 0·7 per cent. of coniine.

The officinal preparations are—the leaves, the fruit, a tincture of the fruit, an extract of the leaves, the juice of the leaves (Succus conii), a compound hemlock pill (composed of extract of hemlock, ipecacuanha, and treacle), an inhalation of coniine (Vapor conii), and a poultice (Cataplasma conii) made with the leaves.

§ 322. Statistics of Coniine Poisoning.—F. A. Falck[346] has been able to collect 17 cases of death recorded in medical literature, up to the year 1880, from either coniine or hemlock. Two of these cases were criminal (murders), 1 suicidal, 2 cases in which coniine had been used medicinally (in one instance the extract had been applied to a cancerous breast; in the other, death was produced from the injection of an infusion of hemlock leaves). The remaining 12 were cases in which the root, leaves, or other portions of the plant had been ignorantly or accidentally eaten.

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§ 323. Effects on Animals.—It destroys all forms of animal life. The author made some years ago an investigation as to its action on the common blow-fly. Droplets of coniine were applied to various parts of blow-flies, which were then placed under glass shades. The symptoms began within a minute by signs of external irritation, there were rapid motions of the wings, and quick and aimless movements of the legs. Torpor set in speedily, the buzz soon ceased, and the insects lay on their sides, motionless, but for occasional twitching of the legs. The wings, as a rule, became completely paralysed before the legs, and death occurred at a rather variable time, from ten minutes to two hours. If placed in a current of air in the sun, a fly completely under the influence of coniine may recover. Coniine causes in frogs, similar to curarine, peripheral paralysis of the motor nerves, combined with a transitory stimulation, and afterwards a paralysis of the motor centres; in frogs the paralysis is not preceded by convulsions. Dragendorff experimented on the action of coniine when given to five cats, the quantities used being ·05 to ·5 grm. The symptoms came on almost immediately, but with the smaller dose given to a large cat, no effect was witnessed until twenty-five minutes afterwards; this was the longest interval. One of the earliest phenomena was dilatation of the pupil, followed by weakness of the limbs passing into paralysis, the hinder legs being affected prior to the fore. The respiration became troubled, and the frequency of the breathing diminished; the heart in each case acted irregularly, and the sensation generally was blunted; death was preceded by convulsions. In the cases in which the larger dose of ·4 to ·5 grm. was administered, death took place within the hour, one animal dying in eight minutes, a second in eighteen minutes, a third in twenty minutes, and a fourth in fifty-eight minutes. With the smaller dose of ·051 grm. given to a large cat, death did not take place until eight hours and forty-seven minutes after administration.

§ 324. Effects on Man.—In a case recorded by Bennet,[347] and quoted in most works on forensic medicine, the symptoms were those of general muscular weakness deepening into paralysis. The patient had eaten hemlock in mistake for parsley; in about twenty minutes he experienced weakness in the lower extremities, and staggered in walking like a drunken man; within two hours there was perfect paralysis of both upper and lower extremities, and he died in three and a quarter hours. In another case, related by Taylor, the symptoms were also mainly those of paralysis, and in other instances stupor, coma, and slight convulsions have been noted.

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§ 325. Physiological Action.—It is generally agreed that coniine paralyses, first the ends of the motor nerves, afterwards their trunks, and lastly, the motor centre itself. At a later period the sensory nerves participate. In the earlier stage the respiration is quickened, the pupils contracted, and the blood-pressure increased; but on the development of paralysis the breathing becomes slowed, the capillaries relaxed, and the blood-pressure sinks. Death takes place from cessation of the respiration, and not primarily from the heart, the heart beating after the breathing has stopped. Coniine is eliminated by the urine, and is also in part separated by the lungs, while a portion is, perhaps, decomposed in the body.

§ 326. Post-mortem Appearances.—There is nothing characteristic in the appearances after death.

Fatal Dose.—The fatal dose of coniine is not accurately known; it is about 150 mgrms. (2·3 grains). In the case of Louise Berger, 10 to 15 drops appear to have caused death in a few minutes. The auto-experiments of Dworzak, Heinrich, and Dillaberger would indicate that one drop may cause unpleasant symptoms. Albers, in the treatment of a woman suffering from cancer of the breast, witnessed convulsions and loss of consciousness from a third dose of 4 mgrms. (·06 grain); and Eulenberg, its full narcotic effects on a child after subcutaneous injection of 1 mgrm. (·015 grain).

§ 327. Separation of Coniine from Organic Matters or Tissues.—The substances are digested with water, acidulated with H₂SO₄, at a temperature not exceeding 40°, and then filtered. If the filtrate should be excessive, it must be concentrated; alcohol is then added, the liquid refiltered, and from the filtrate the alcohol separated by distillation.

On cooling, the acid fluid is agitated with benzene, and the latter separated in the usual way. The fluid is now alkalised with ammonia, and shaken up once or twice with its own volume of petroleum ether; the latter is separated and washed with distilled water, and the alkaloid is obtained almost pure. If the petroleum ether leaves no residue, it is certain that the alkaloid was not present in the contents of the stomach or intestine.

The affinity of coniine with ether or chloroform is such, that its solution in either of these fluids, passed through a dry filter, scarcely retains a drop of water. In this way it may be conveniently purified, the impurities dissolved by water remaining behind.

In searching for coniine, the stomach, intestines, blood, urine, liver, and lungs are the parts which should be examined. According to Dragendorff, it has been discovered in the body of a cat six weeks after death.

Great care must be exercised in identifying any volatile alkaloid as coniine, for the sources of error seem to be numerous. In one case[348] a volatile coniine-like ptomaine, was separated from a corpse, and thought to be coniine; but Otto found that in its behaviour to platinic chloride, it differed from coniine; it was very poisonous—·07 was fatal to a frog, ·44 to a pigeon, in a few minutes. In the seeds of Lupinus luteus there is a series of coniine-like substances,[349] but they do not give the characteristic crystals with hydrochloric acid.

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2. TOBACCO—NICOTINE.

§ 328. The different forms of tobacco are furnished by three species of the tobacco plant, viz., Nicotianum tabacum, N. rustica, and N. persica.

Havanna, French, Dutch, and the American tobaccos are in the main derived from N. tabacum; Turkish, Syrian, and the Latakia tobaccos are the produce of N. rustica. There seems at present to be little of N. persica in commerce.

All the species of tobacco contain a liquid, volatile, poisonous alkaloid (Nicotine), probably united in the plant with citric and malic acids. There is also present in tobacco an unimportant camphor (nicotianin). The general composition of the plant may be gathered from the following table:—

TABLE SHOWING THE COMPOSITION OF FRESH LEAVES OF TOBACCO
(POSSELT AND RIENMANN).

Nicotine,			0·060
Concrete volatile oil,			0·010
Bitter extractive,			2·870
Gum with malate of lime,			1·740
Chlorophyl,			0·267
Albumen and gluten,			1·308
Malic acid,			0·510
Lignine and a trace of starch,			4·969
Salts (sulphate, nitrate, and malate of potash, chloride of potassium, phosphate and malate of lime, and malate of ammonia,)		-	0·734
Silica,			0·088
Water,			88·280
			100·836

§ 329. Quantitative Estimation of Nicotine in Tobacco.—The best process (although not a perfectly accurate one) is the following:—25 grms. of the tobacco are mixed with milk of lime, and allowed to stand until there is no odour of ammonia; the mixture is then exhausted by petroleum ether, the ether shaken up with a slight excess of normal sulphuric acid, and titrated back by baryta water; the sulphate of baryta may be collected and weighed, so as to control the results. With regard to the percentage of nicotine in commercial tobacco, Kosutany found from 1·686 to 3·738 per cent. in dry tobacco; Letheby, in six samples, from 1·5 to 3·2 per cent.; whilst Schlössing gives for Havanna 2 per cent., Maryland 2·29 per cent., Kentucky 6·09 per cent., Virginian 6·87 per cent., and for French tobacco, quantities varying from 3·22 to 7·96 per cent. Again, Lenoble found in Paraguay tobacco from 1·8 to 6 per cent.; and Wittstein, in six sorts of tobacco in Germany, 1·54 to 2·72 per cent.

Mr. Cox[350] has recently determined the amount of nicotine in a number of tobaccos. The results are tabulated in the following table as follows:—

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TABLE OF RESULTS, ARRANGED ACCORDING TO PER CENT. OF NICOTINE.

	Variety examined.	Nicotine per cent.
1.	Syrian leaves (a),		·612
2.	American chewing,		·935
3.	Syrian leaves (b),	1	·093
4.	Chinese leaves,	1	·902
5.	Turkish (coarse cut),	2	·500
6.	Golden Virginia (whole strips),	2	·501
7.	Gold Flake (Virginia),	2	·501
8.	“Navy-cut” (light coloured),	2	·530
9.	Light returns (Kentucky),	2	·733
10.	“Navy-cut” (dark “all tobacco”),	3	·640
11.	Best “Birds-eye,”	3	·931
12.	Cut Cavendish (a),	4	·212
13.	“Best Shag” (a),	4	·907
14.	“Cut Cavendish” (b),	4	·970
15.	“Best Shag” (b),	5	·000
16.	French tobacco,	8	·711
17.	Algerian tobacco (a),	8	·813
18.	Algerian tobacco (b),	8	·900

It is therefore obvious that the strength of tobacco in nicotine varies between wide limits.

Twenty-five grammes (or more or less, according to the amount of the sample at disposal) of the dried and powdered tobacco were intimately mixed with slaked lime, and distilled in a current of steam until the condensed steam was no longer alkaline; the distillate was slightly acidulated with dilute H₂SO₄, and evaporated to a conveniently small bulk. This was made alkaline with soda, and agitated repeatedly with successive portions of ether. The separated batches of ethereal solution of nicotine were then mixed and exposed to the air in a cool place. This exposure to the air carries away ammonia, if any be present, as well as ether.

Water was added to the ethereal residue, and the amount of nicotine present determined by decinormal H₂SO₄, using methyl-orange as an indicator. One c.c. of decinormal H₂SO₄ represents 0·0162 gramme of nicotine (C₁₀H₁₄N₂).

§ 330. Nicotine (C₁₀H₁₄N₂).—Hexahydro dipyridyl (C₅H₄N)₂H₆, when pure, is an oily, colourless fluid, of 1·0111, specific gravity at 15°.[351] It evaporates under 100° in white clouds, and boils at about 240°, at which temperature it partly distils over unchanged, and is partly decomposed—a brown resinous product remaining. It volatilises with aqueous and amyl alcohol vapour notably, and is not even fixed at -10°. It has a strong alkaline reaction, and rotates a ray of polarised light to the right. Its odour, especially on warming, is strong and unpleasantly like tobacco, and it has a sharp caustic taste. It absorbs water exposed to the air, and dissolves in water in all proportions, partly separating from such solution on the addition of a caustic alkali. The aqueous solution acts in many respects like ammonia, saturating acids fully, and may therefore be in certain cases estimated with accuracy by titration, 49 parts of H₂SO₄ corresponding to 162 of nicotine. It gives on oxidation nicotinic acid = m(β) pyridincarbo acid C₅H₄N(COOH), and by oxidation with elimination of water dipyridyl (C₅H₄N)₂, and through reduction dipiperydil (C₅H₁₀N)₂.

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Alcohol and ether dissolve nicotine in every proportion; if such solutions are distilled, nicotine goes over first. The salts which it forms with hydrochloric, nitric, and phosphoric acids crystallise with difficulty; tartaric and oxalic acid form white crystalline salts, and the latter, oxalate of nicotine, is soluble in alcohol, a property which distinguishes it from the oxalate of ammonia. The best salts are the oxalate and the acid tartrate of nicotine, from which to regenerate nicotine in a pure state.

Hydrochloride of nicotine is more easily volatilised than the pure base. Nicotine is precipitated by alkalies, &c., also by many oxyhydrates, lead, copper, &c. By the action of light, it is soon coloured yellow and brown, and becomes thick, in which state it leaves, on evaporation, a brown resinous substance, only partly soluble in petroleum ether.

A very excellent test for nicotine, as confirmatory of others, is the beautiful, long, needle-like crystals obtained by adding to an ethereal solution of nicotine a solution of iodine in ether. The crystals require a few hours to form.

Chlorine gas colours nicotine blood-red or brown; the product is soluble in alcohol, and separates on evaporation in crystals.

Cyanogen also colours nicotine brown; the product out of alcohol is not crystalline. Platin chloride throws down a reddish crystalline precipitate, soluble on warming; and gallic acid gives a flocculent precipitate. A drop of nicotine poured on dry chromic acid blazes up, and gives out an odour of tobacco camphor; if the ignition does not occur in the cold, it is produced by a gentle heat. It is scarcely possible to confound nicotine with ammonia, by reason of its odour; and, moreover, ammonia may always be excluded by converting the base into the oxalate, and dissolving in absolute alcohol.

On the other hand, a confusion between coniine and nicotine is apt to occur when small quantities only are dealt with. It may, however, be guarded against by the following tests:—

(1.) If coniine be converted into oxalate, the oxalate dissolved in alcohol, and coniine regenerated by distillation (best in vacuo) with caustic lye, and then hydrochloric acid added, a crystalline hydrochlorate of coniine is formed, which doubly refracts light, and is in needle-shaped or columnar crystals, or dendritic, moss-like forms. The columns afterwards become torn, and little rows of cubical, octahedral, and tetrahedral crystals (often cross or dagger-shaped) grow out of yellow amorphous masses. Crystalline forms of this kind are rare, save in the case of dilute solutions of chloride of ammonium (the presence of the latter is, of course, rendered by the treatment impossible); and nicotine does not give anything similar to this reaction.

(2.) Coniine coagulates albumen; nicotine does not.

(3.) Nicotine yields a characteristic crystalline precipitate with an aqueous solution of mercuric chloride; the similar precipitate of coniine is amorphous.

(4.) Nicotine does not react with CS₂ to form thiosulphate (see p. 266).

§ 331. Effects on Animals.—Nicotine is rapidly fatal to all animal life—from the lowest to the highest forms. That tobacco-smoke is inimical to insect-life is known to everybody; very minute quantities in water kill infusoria. Fish of 30 grms. weight die in a few minutes from a milligram of nicotine; the symptoms observed are rapid movements, then shivering and speedy paralysis, with decreased motion of the gills, and death. With frogs, if doses not too large are employed, there is first great restlessness, then strong tetanic convulsions, and a very peculiar position of the limbs; the respiration after fatal doses soon ceases, but the heart beats even after death. Birds also show tetanic convulsions followed by paralysis and speedy death. The symptoms witnessed in mammals poisoned by nicotine are not essentially dissimilar. With large doses the effect is similar to that of prussic acid—viz., a cry, one or two shuddering convulsions, and death. If the dose is not too large, there is trembling of the limbs, excretion of fæces and urine, a peculiar condition of stupor, a staggering gait, and then the animal falls on its side. The respiration, at first quickened, is afterwards slowed, and becomes deeper than natural; the pulse, also, with moderate doses, is first slowed, then rises in frequency, and finally, again falls. Tetanic convulsions soon develop, during the tetanus the pupils have been noticed to be contracted, but afterwards dilated, the tongue and mouth are livid, and the vessels of the ear dilated. Very characteristic of nicotine poisoning as witnessed in the cat, the rabbit, and the dog, is its peculiarly violent action, for after the administration of from one to two drops, the whole course from the commencement of symptoms to the death may take place in five minutes. F. Vas has drawn the smoke of tobacco from an immense pipe, and condensed the products; he finds the well-washed tarry products without physiological action, but the soluble liquid affected the health of rabbits,—they lost weight, the number of the blood corpuscles was decreased, and the hæmoglobin of the blood diminished.[352]

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The larger animals, such as the horse, are affected similarly to the smaller domestic animals. A veterinary surgeon, Mr. John Howard, of Woolwich,[353] has recorded a case in which a horse suffered from the most violent symptoms of nicotine-poisoning, after an application to his skin of a strong decoction of tobacco. The symptoms were trembling, particularly at the posterior part of the shoulders, as well as at the flanks, and both fore and hind extremities; the superficial muscles were generally relaxed and felt flabby; and the pupils were widely dilated. There was also violent dyspnœa, the respirations being quick and short, pulse 32 per minute, and extremely feeble, fluttering, and indistinct. When made to walk, the animal appeared to have partly lost the use of his hind limbs, the posterior quarter rolling from side to side in an unsteady manner, the legs crossing each other, knuckling over, and appearing to be seriously threatened with paralysis. The anus was very prominent, the bowels extremely irritable, and tenesmus was present. He passed much flatus, and at intervals of three or four minutes, small quantities of fæces in balls, partly in the liquid state, and coated with slimy mucus. There was a staring, giddy, intoxicated appearance about the head and eyes, the visible mucous membrane being of a dark-red colour. A great tendency to collapse was evident, but by treatment with cold douches and exposure to the open air, the horse recovered.

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In a case occurring in 1863, in which six horses ate oats which had been kept in a granary with tobacco, the symptoms were mainly those of narcosis, and the animals died.[354]

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§ 332. Effects on Man.—Poisoning by the pure alkaloid nicotine is so rare that, up to the present, only three cases are on record. The first of these is ever memorable in the history of toxicology, being the first instance in which a pure alkaloid had been criminally used. The detection of the poison exercised the attention of the celebrated chemist Stas. I allude, of course, to the poisoning of M. Fougnies by Count Bocarmé and his wife. For the unabridged narrative of this interesting case the reader may consult Tardieu’s Étude Médico-Légale sur L’Empoisonnement.

Bocarmé actually studied chemistry in order to prepare the alkaloid himself, and, after having succeeded in enticing his victim to the chateau of Bitremont, administered the poison forcibly. It acted immediately, and death took place in five minutes. Bocarmé now attempted to hide all traces of the nicotine by pouring strong acetic acid into the mouth and over the body of the deceased. The wickedness and cruelty of the crime were only equalled by the clumsy and unskilful manner of its perpetration. The quantity of nicotine actually used in this case must have been enormous, for Stas separated no less than ·4 grm. from the stomach of the victim.

The second known case of nicotine-poisoning was that of a man who took it for the purpose of suicide. The case is related by Taylor. It occurred in June 1863. The gentleman drank an unknown quantity from a bottle; he stared wildly, fell to the floor, heaving a deep sigh, and died quietly without convulsion. The third case happened at Cherbourg,[355] where an officer committed suicide by taking nicotine, but how much had been swallowed, and what were the symptoms, are equally unknown, for no one saw him during life.

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Poisoning by nicotine, pure and simple, then is rare. Tobacco-poisoning is very common, and has probably been experienced in a mild degree by every smoker in first acquiring the habit. Nearly all the fatal cases are to be ascribed to accident; but criminal cases are not unknown. Christison relates an instance in which tobacco in the form of snuff was put into whisky for the purpose of robbery. In 1854, a man was accused of attempting to poison his wife by putting snuff into her ale, but acquitted. In another case, the father of a child, ten weeks old, killed the infant by putting tobacco into its mouth. He defended himself by saying that it was applied to make the child sleep.

In October 1855,[356] a drunken sailor swallowed (perhaps for the purpose of suicide) his quid of tobacco, containing from about half an ounce to an ounce. He had it some time in his mouth, and in half an hour suffered from frightful tetanic convulsions. There was also diarrhœa; the pupils were dilated widely; the heart’s action became irregular; and towards the end the pupils again contracted. He died in a sort of syncope, seven hours after swallowing the tobacco.

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§ 333. In 1829 a curious instance of poisoning occurred in the case of two girls, eighteen years of age, who suffered from severe symptoms of tobacco-poisoning after drinking some coffee. They recovered; and it was found that tobacco had been mixed with the coffee-berries, and both ground up together.[357]

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Accidents have occurred from children playing with old pipes. In 1877[358] a child, aged three, used for an hour an old tobacco-pipe, and blew soap bubbles with it. Symptoms of poisoning soon showed themselves, and the child died in three days.

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Tobacco-juice, as expressed or distilled by the heat developed in the usual method of smoking, is very poisonous. Sonnenschein relates the case of a drunken student, who was given a dram to drink, into which his fellows had poured the juice from their pipes. The result was fatal. Death from smoking is not unknown.[359] Helwig saw death follow in the case of two brothers, who smoked seventeen and eighteen German pipefuls of tobacco. Marshall Hall[360] records the case of a young man, nineteen years of age, who, after learning to smoke for two days, attempted two consecutive pipes. He suffered from very serious symptoms, and did not completely recover for several days. Gordon has also recorded severe poisoning from the consecutive smoking of nine cigars. The external application of the leaf may, as already shown in the case of the horse, produce all the effects of the internal administration of nicotine. The old instance, related by Hildebrand, of the illness of a whole squadron of hussars who attempted to smuggle tobacco by concealing the leaf next to their skin, is well known, and is supported by several recent and similar cases. The common practice of the peasantry, in many parts of England, of applying tobacco to stop the bleeding of wounds, and also as a sort of poultice to local swellings, has certainly its dangers. The symptoms—whether nicotine has been taken by absorption through the broken or unbroken skin, by the bowel, by absorption through smoking, or by the expressed juice, or the consumption of the leaf itself—show no very great difference, save in the question of time. Pure nicotine acts with as great a rapidity as prussic acid; while if, so to speak, it is entangled in tobacco, it takes more time to be separated and absorbed; besides which, nicotine, taken in the concentrated condition, is a strong enough base to have slight caustic effects, and thus leaves some local evidences of its presence. In order to investigate the effects of pure nicotine, Dworzak and Heinrich made auto-experiments, beginning with 1 mgrm. This small dose produced unpleasant sensations in the mouth and throat, salivation, and a peculiar feeling spreading from the region of the stomach to the fingers and toes. With 2 mgrms. there was headache, giddiness, numbness, disturbances of vision, torpor, dulness of hearing, and quickened respirations. With 3 to 4 mgrms., in about forty minutes there was a great feeling of faintness, intense depression, weakness, with pallid face and cold extremities, sickness, and purging. One experimenter had shivering of the extremities and cramps of the muscles of the back, with difficult breathing. The second suffered from muscular weakness, fainting, fits of shivering, and creeping sensations about the arms. In two or three hours the severer effects passed away, but recovery was not complete for two or three days. It is therefore evident, from these experiments and from other cases, that excessive muscular prostration, difficult breathing, tetanic cramps, diarrhœa, and vomiting, with irregular pulse, represent both tobacco and nicotine poisoning. The rapidly-fatal result of pure nicotine has been already mentioned; but with tobacco-poisoning the case may terminate lethally in eighteen minutes. This rapid termination is unusual, with children it is commonly about an hour and a half, although in the case previously mentioned, death did not take place for two days.

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§ 334. Physiological Action.—Nicotine is absorbed into the blood and excreted unchanged, in part by the kidneys and in part by the saliva (Dragendorff). According to the researches of Rosenthal and Krocker,[361] nicotine acts energetically on the brain, at first exciting it, and then lessening its activity; the spinal marrow is similarly affected. The convulsions appear to have a cerebral origin; paralysis of the peripheral nerves follows later than that of the nerve centres, whilst muscular irritability is unaffected. The convulsions are not influenced by artificial respiration, and are therefore to be considered as due to the direct influence of the alkaloid on the nervous system. Nicotine has a striking influence on the respiration, first quickening, then slowing, and lastly arresting the respiratory movements: section of the vagus is without influence on this action. The cause of death is evidently due to the rapid benumbing and paralysis of the respiratory centre. Death never follows from heart-paralysis, although nicotine powerfully influences the heart’s action, small doses exciting the terminations of the vagus in the heart, and causing a slowing of the beats. Large doses paralyse both the controlling and exciting nerve-centres of the heart; the heart then beats fast, irregularly, and weakly. The blood-vessels are first narrowed, then dilated, and, as a consequence, the blood-pressure first rises, then falls. Nicotine has a special action on the intestines. As O. Nasse[362] has shown, there is a strong contraction of the whole tract, especially of the small intestine, the lumen of which may be, through a continuous tetanus, rendered very small. This is ascribed to the peripheral excitation of the intestinal nerves and the ganglia. The uterus is also excited to strong contraction by nicotine; the secretions of the bile and saliva are increased.

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