in the vacuum obtained by a water-pump as long as the liquid remains limpid. It is now strained and the residue washed with a little solvent of about the same alcoholic content as the filtrate. The latter, if too much loaded with tissue matters, so as to cause the liquid to emulsify in shaking out afterward, may be treated with full-strength alcohol, filtered-better by use of a filter-pump and a Buechner funnel-and the filtrate concentrated as before.

The extraction, however varied, should be so governed as to avoid, so far as possible, the conditions of hydrolysis.

The final aqueous liquid, which may be slightly alcoholic, filtered clear, is gently shaken in a separator with chloroform, then made only perceptibly alkaline by the addition of ammonia, again shaken (not so violently as to cause emulsification) for about five minutes, when the crude chloroform extract is drawn off, and in the same way a second and a third portion obtained. The total crude chloroform extract is now shaken out with water very slightly acidulated with sulphuric acid in three portions, and at once the total water solution is shaken with chloroform, then made just alkaline with ammonia, and shaken successively with three portions of chloroform. If, on evaporation, a small portion of the last chloroform extract shows the presence of obstructing tissue. matter, the purification is repeated, beginning with the treatment by acidulated water, until a purified chloroform extract is obtained. This is to be concentrated, and then portions of a drop or two or three are separately evaporated to dryness for final tests, as specified under the head of Chemical Tests.

To estimate the quantity of atropin in the extract, its precipitation as a periodid, in the gravimetric method, is probably the most expedient way. The alkaloidal solution is added to an excess of decinormal aqueous iodin solution with potassium iodid, the precipitate well stirred, drained, washed, dried, and weighed as atropin hydriodid octaiodid. When this weight is multiplied by 0.202, the product expresses the quantity of atropin as free alkaloid. Any estimate of the quantity of atropin in the tissues must depend upon an estimation of the loss of the alkaloid in the process of extraction, and if this be more than conjecture, it must be based upon the loss of alkaloid in a parallel analysis made for control.

Deposition in the Body.-Wormley recovered atropin from the blood after administering the drug to dogs and cats. The tropeins generally appear in the urine of persons poisoned by them. Atropin has been repeatedly recovered from putrefactive animal tissues, in which it does not readily decompose. After its administration, Dragendorff detected atropin in the urine, in the liver, and in the kidneys of the cat, but none was found in the spleen. It was found in the blood of a cat, weighing 6 pounds (2800 gm.), twenty-four hours after 2.8 grains

1 The apparatus shown in Fig. 29, p. 336, is useful for this purpose.

2 Prescott and Gordin, "Atropin Periodids," etc., Jour. Amer. Chem. Soc., 1898, vol. xx., p. 329; ibid., Volumetric Estimation of Alkaloids, etc., vol. xx., pp.

712, 722, 724.

(0.1863 gm.) of the alkaloid had been administered by the mouth, with ligation of the esophagus. The same investigator gave 1 grain (0.06 gm.) of atropin daily to a rabbit of 3 pounds (1500 gm.). Each day the urine was found to contain much atropin. On the tenth day the blood was tested and mere traces of the alkaloid found in it. In a similar experiment like results were obtained in the urine, but no alkaloid was found in the feces.

COCAIN, ALKALOID OF THE COCA-LEAF.

General Description.-Cocain is manufactured from the leaf of Erythroxylon coca of South America, and constitutes about 0.75 per cent. of the freshly dried leaf. Coca-leaf and its liquid preparations are furnished in pharmacy, but they are hardly known as a source of poisoning, and the same is true of the minor alkaloids of the leaf. Cocain, usually as the hydrochlorid, is in common use as a local anesthetic. It is a white, crystalline solid of a bitter taste, and, as a salt, is freely soluble in water or alcohol. Its chemical formula is C,,H,,NO,. It is most used as the hydrochlorid of cocain, CH, NO,HC1.2H2O, which is of variable crystalline or amorphous forms. Applied to the mucous membrane it causes a local insensibility to pain or injury. Crude cocain is shipped to manufacturers from South America, but is not found in the retail market.

17

Symptoms of Poisoning by Cocain. Whether taken by the mouth, hypodermically, or by absorption through an abraded surface or a portion of the mucous membrane, if a poisonous quantity be taken into the system, severe symptoms quickly appear. There are excitement, fulness and pain in the head, dryness and burning in the throat and nose, and burning pain in the stomach. The pulse is quickened at first, and later becomes feeble and slow. The respirations at first usually are quickened, becoming slow and labored, with cold extremities and a bluish face. The pupils of the eyes are commonly dilated for a time. Cases are on record showing great deviations from the symptoms just described.

Chronic poisoning, with which may be classed the effects of the cocain habit, is a subject for the physician rather than for the toxicologist.

Period when Fatal.-In acute poisoning by cocain the symptoms appear very quickly after the poison is absorbed and run a rapid course. It is stated that, generally, if the patient survives half an hour, he recovers (see the cases quoted below).

Fatal Quantity.—(See the Cases of poisoning given below, especially Cases 1 to 8.)

Treatment. When the poison has been taken by the mouth, the first thing to do is to draw off the contents of the stomach by means of a siphon-tube or a stomach-pump, introducing water and drawing it off again, until the stomach is well washed out. If it can be done with

1 Walter S. Haines in Hamilton's Legal Medicine, vol. i., p. 428.

out delay, finely powdered charcoal may be administered during the evacuation of the stomach.

The symptoms, variable as they are, should be met by the restorative measures directly indicated. Carbonate of ammonium, hot alcoholic drinks, stimulants hypodermically, sinapisms over the heart and stomach, and friction of the extremities are helpful, especially in the cyanotic stage. Professor Haines states that "inhalations of amyl nitrite and hypodermic injections of nitroglycerin are often signally useful; and inhalations of pure oxygen are very valuable in relieving threatened asphyxia. In case breathing ceases, artificial respiration should be resorted to, and electricity may be tried, with some chance of a favorable result."

CASES OF POISONING BY COCAIN.

CASES 1-3.-One dram (4 c.c.) of a 4 per cent. solution of cocain (about 24 grains-0.146 gm.—of the alkaloid) was thrown into the urethra of a man. Convulsions appeared at once, and death occurred in four minutes. The autopsy showed intense congestion of the lungs.

A 4 per cent. solution of cocain was freely applied to the face of a young woman who was treated for facial blemish. The patient walked to the window and fell dead.

Forty minims (2.5 c.c.) of a 4 per cent. solution of cocain (about 13 grains0.097 gm. of the alkaloid) were injected into the seat of rectal fistula of a man of twenty-six years. In three minutes he became unconscious and convulsed, and

one minute later died."

CASE 4.—Half a grain (0.032 gm.) of cocain was injected into the gum. The patient, a woman, became wildly delirious, the pupils were dilated, the extremities cold, the respirations hurried and irregular. Treatment by injections of brandy and ether into the rectum was followed by recovery.

CASE 5.-One grain (0.065 gm.) was injected into an external hemorrhoid which was to be removed. The pulse became indistinguishable, the heart-beats 40 a minute, the hands and arms in a strong clonic spasm, the extremities cold, the pupils widely dilated, and the urine suppressed. Patient recovered.*

CASE 6.-Twenty drops of a 6 per cent. solution of cocain (about 1} grains0.078 gm. of the alkaloid) were given a man hypodermically. There was sudden collapse, with great dilatation of the pupils, quickened breathing, irregular pulse of 160, symptoms from which the patient recovered.

CASE 7.-A man took 44 grains (0.312 gm.) of cocain hydrochlorid. Symptoms: failure of eyesight, loss of use of the legs-appeared like a drunken mancramps in the abdomen, pulse from 80 to 86, profuse sweating. Recovery followed in six days.

CASE 7a.-A man of twenty-four years took 8 or 9 grains (over 0.5 gm.) of cocain hydrochlorid. The symptoms included numbness in the mouth, tongue, and throat, extending later to the stomach and abdomen, also muscular movements resembling those of a bad case of chorea, the movements, however, being slower and more regular. Treatment: nitrite of amyl, calomel, castor oil. Recovery.

CASE 8.-A man suffering from disease of kidneys took 20 grains (1.3 gm.) of cocain and died an hour after. At the autopsy the lungs were found congested, as were the brain and the underlying part of the stomach. There was blood-clot in the heart. It was inferred that death occurred from paralysis of both the cardiac and respiratory centers.

Walter S. Haines in Hamilton's Legal Medicine, vol. i., p. 429.

2 J. B. Mattison, Dublin Jour. Med. Sci., 1895, vol. xcix., p. 116.

3 C. E. Gooding, Lancet, London, 1888, vol. i., p. 394.

J. Miller, New York Med. Jour., 1894, vol. lx., p. 660.

5 N. Teeter, Therap. Gaz., 1895, vol. xix., p. 11.

6 C. S. Kilhman, Lancet, London, 1887, vol. i., p. 17.
Ibid., London, 1889, vol. i., p. 292.

CASE 9.—A girl of sixteen years took about 10 grains (0.64 gm.) of cocain in 10 per cent. solution on an empty stomach and then drank hot tea. Death occurred in forty minutes.'

CASE 10.-A girl of seventeen years took from 12 to 15 grains (almost 1 gm.) of cocain and died in forty minutes. At the autopsy the pupils were found dilated, the heart-valves normal, with a small quantity of dark, fluid blood in the right ventricle, the left ventricle being empty, the lungs congested and highly crepitant, the brain anemic but its meninges engorged, the liver, spleen, and kidneys hyperemic, the bladder containing 3 or 4 ounces of urine."

CASE 11.-A girl took a teaspoonful of cocain in a glass of beer and died in great pain half an hour after. At the autopsy the brain, pons, and medulla were found engorged, and there was red serum in the side ventricles. The liver, kidneys, and spleen were congested. The stomach contained dark-red mucus, yielding plain chemical tests for cocain.

Postmortem Appearances.-An excess of blood has been found in the brain, liver, kidneys, and also in the lungs. The blood has been found dark and fluid. These appearances, however, are not especially characteristic of death from this poison (see Cases 8, 10, 11).

Chemical Tests.-Cocain is both a methyl- and a benzoyl-ester of ecgonin, and therefore yields to hydrolysis or saponification, giving first methyl-alcohol and then benzoic acid. Ecgonin is a base corresponding to atropin. With this well-ascertained structure, however, no delicate and distinctive chemical tests have as yet been elaborated for cocain. Reliance may best be placed upon-(1) Physiologic tests; (2) the test for benzoic acid ; (3) the crystalline form of the gold chlorid.

1. Physiologic Tests. For these a neutral solution of a salt of the alkaloid is employed. Brought by a glass rod into contact with the tongue or lip, repeating the contact upon the same spot, cocain gives a sense of numbness and a characteristic insensibility to touch. (If not too dilute, there is a slight bitterness of taste.) With full effect there is a blanching of the color of the mucous membrane. The cessation of sensation lasts but a few minutes unless the application be repeated. A solution of 4 per cent. causes both numbness and blanching in marked degree. The strength of a solution obtained in analysis should be judged by comparison with graded solutions of known strength of cocain upon the same subject. Upon the eye the anesthetic and blanching effects upon the conjunctiva are obtained, and an additional test, that of dilatation of the pupil; this effect is not so extreme as that of atropin, and much less persistent.

2. The Test for Benzoic Acid.-Unless made with drop quantities and the use of a magnifier, this test must fail from lack of delicacy in ordinary analysis for poisons left in the body after death. To a wellconcentrated, clear, aqueous solution-which need not exceed one drop -on a glass slide, add about one-tenth its volume of concentrated sulphuric acid, and heat the liquid on the water-bath for about five minAdd concentrated ammonia from a capillary pipet to nearly neutralize, making sure, by a minute slip of litmus-paper, that the reaction is not alkaline. Now add from the capillary tube a very little

utes.

JG. M. Johnston, Brit. Med. Jour., 1895, vol. ii., p. 1162.
2 O. H. Garland, Lancet, London, 1895, vol. ii., p. 1104.

ferric chlorid solution. A buff-colored precipitate should be obtained if cocain was present in sufficient quantity in the liquid taken. Ferric benzoate is not soluble in very dilute acetic acid. The slide may be placed alternately over white and black ground, under the magnifier, in judging of the result. A control test should be made.

3. The Gold Chlorid Test.-A solution of cocain hydrochlorid, which

may be prepared by careful treatment of a film of residue of the free alkaloid with a drop or two of very dilute hydrochloric acid, is at once precipitated by auric chlorid when the alkaloidal solution is as strong as 1:3000. Under the microscope stellate crystals are discerned. In solutions of 112,000 the crystals are obtained. The test should be conducted on the scale indicated in the preceding paragraph, and if the precipitate be amorphous, it should be warmed, and then, if necessary, diluted, to obtain the crystals upon gradual cooling. Free cocain crystallizes in monoclinic prisms melting at from 97° to 98° C.

Separation from Animal Tissues.-The method of extraction directed for atropin (p. 469) is suitable for cocain. Instead of chloroform as an immiscible solvent, benzene may be employed.

According to Sonnie-Moret,' cocain is somewhat quickly changed in the living organism, and unless taken in considerable quantities, toxicologic examination will give negative results.

COLCHICUM AND ITS ALKALOID, COLCHICIN.

Colchicum autumnale, the meadow-saffron, owes its poisonous effects chiefly to the alkaloid colchicin, the distinctive chemical product of the plant. Both the seed and the corm (root) are used in medicine and are liable to act as poison. From 0.2 to 0.4 per cent. of the alkaloid has been found in the seed; from 0.08 to 0.2 per cent. in the root; from 0.01 to 0.02 per cent. in the fresh flowers, and 0.003 per cent. in the fresh leaves. The drug is an importation in the United States from plants collected in the temperate regions of Europe and northern Africa. It was known to the ancients as a poison and as a remedy. The tineture of the seed, the fluid extract of the root and of the seed, and the wine of the root and of the seed are pharmacopeial preparations in medicinal use. There is also a solid extract directed to be made from

1

Inaug. Diss., Jahresb. d. Pharm., vol. xxvii., p. 390; Chem. Centralbl., 1893, vol. i., p. 859.