ACONITE: ACONITIA OR ACONITINE.

Plants: Aconitum napellus—A. ferox. Alkaloids: Aconitia—Pseudaconitia—other bases—Decompositions—Proportions in the plants. Commercial aconitia—German aconitia—English aconitia. Separation—Tests, chemical and physiological. History—Preparations, official and non-official. Physiological effects—Causes of death—Post mortem appearances—Treatment and antidotes—Remarks—Phosphoric acid test—Case referred to by Dr. Stevenson.

The name aconite is applied to a great number of plants belonging to the natural order RanunculaceÆ. Two species only need be noticed here, Aconitum napellus and A. ferox. The former is the well-known “monkshood,” “wolfsbane,” or “blue rocket,” a very beautiful but exceedingly poisonous plant, commonly cultivated in English gardens. This very variable and widely diffused species is found in the mountainous districts of the temperate regions of the northern hemisphere: it occurs in the Alps up to an altitude of more than 6,000 feet, in the Pyrenees, and in the mountain ranges of Germany and Austria. It is also met with in Sweden, Denmark, Siberia, and in the mountainous districts on the Pacific coast of North America.

Aconitum ferox, Nepaul aconite —“Bikh”), is a native of the subalpine Himalayas, occurring, together with A. napellus and several other poisonous species, at an elevation of 10,000 to 14,000 feet.

The most recent researches of Dr. C. R. Alder Wright and others have shown that Aconitum napellus chiefly owes its poisonous properties to the base aconitia, or aconitine (also called aconitina), C₃₃ H₄₃ NO₁₂, a highly active crystallizable alkaloid furnishing readily crystallizable salts. This base constitutes about one-half of the total quantity of alkaloids present in the root, and is considered to be in combination with aconitic acid, H₃ C₆ H₃ O₆. There is also present, but in much smaller quantity (about 10 per cent. of the total bases present—Wright), another physiologically active crystallizable alkaloid, pseudaconitia, C₃₆ H₄₉ NO₁₂, similar in many respects to aconitia (especially in its effects upon the animal system), but not so readily yielding crystallizable salts. The roots of A. napellus contain, in addition to aconitia and pseudaconitia, a considerable quantity of a third base, comparatively inert, apparently amorphous, yielding non-crystallizable salts, and containing a higher percentage of carbon than either aconitia or pseudaconitia.

Aconitum ferox contains as its active principle pseudaconitia, or nepaline, associated with a comparatively small quantity of aconitia: there is present in addition a non-crystallizable alkaloid containing more carbon than either of the other bases, but apparently not identical with the analogous body from A. napellus.

The plants have been stated to contain, besides the bases already named, various other alkaloids, such as “napel-line,” “acolyctine,” “lycoctonine,” &c., but there is no doubt that these substances are merely products of the decomposition of aconitia and pseudaconitia, formed during the process of extraction. Aconitia and pseudaconitia are very easily decomposed; thus, when heated with water in a sealed tube, the former is converted into benzoic acid and a fresh alkaloid, aconine, C₂₆ H₃₉ NO₁₁, the reaction being represented by the following equation:—

Pseudaconitia, so treated, yields dimethyl-protocatechuic (or “veratric”) acid and a new base, pseudaconine, C₂₇ H₄₁ NO₉, the equation being:—

Aconine is doubtless identical with HÜbschmann’s “napel-line,” discovered by him in commercial aconitia, and afterwards proved to be the same as the “acolyctine” which he had previously obtained. Pseudaconine is apparently the base “lycoctonine” of the same chemist.

Commercial aconitia is a mixture of aconitia and pseudaconitia with variable quantities of their decomposition-products, aconine and pseudaconine, and of the amorphous unnamed alkaloids above referred to (Wright and others; Year-Book of Pharmacy, 1877, et seq.). In commercial aconitia prepared from Aconitum napellus (German aconitia), aconitia predominates: English aconitia is chiefly if not entirely prepared from A. ferox, and in it pseudaconitia is the prevailing active base.

All parts of the plants (A. napellus and A. ferox) are poisonous, the active principles being contained in the seeds, roots, leaves and flowering tops. The roots are chiefly used for the extraction of the alkaloids, of which the proportions yielded are very variable and depend on the time when the roots are collected. An ounce of the fresh root of A. napellus contains, according to Woodman and Tidy, from ¼ to ¾ of a grain of aconitia, while a pound of the dried root furnishes from 12 to 36 grains, or 0·1 to 0·2 per cent. “The average produce of the root, collected after flowering and fresh, is 8·58 grains of aconitia in the pound; of the same dried, 35·72 grains. But if collected before flowering, the yield is only 3·5 grains per pound in the fresh, and 12·13 in the dried root (Herapath). These results are the average of several experiments.... The root of A. ferox contains about three times as much alkaloid as that of the English plant” (Royle’s Mat. Med.). According to Wright and Rennie (Year-Book of Pharm., 1880, 458), the percentage of total bases yielded by the root of A. napellus, calculated on the dry substance, amounted to ·07 per cent., equivalent to about ·05 per cent, of total alkaloids in the dry herb. Two-fifths of the total alkaloid consisted of pure crystallized aconitia.

Commercial aconitia or aconitine is generally met with as a white amorphous powder, but is occasionally crystalline. It dissolves in 150 parts of cold and 50 parts of hot water, and is also soluble in alcohol, benzole, and chloroform: it is inodorous, possesses an acrid taste (W. and T., For. Med., p. 392), and is strongly alkaline to test-paper. It generally fuses below 100° C. (60° C., W. and T.), and gives an amorphous sublimate above 150° C. (pure aconitia fuses at 183°-184° C.: pure pseudaconitia melts at 104°-105° C.): when strongly heated with free access of air, it burns with a yellow, smoky flame, leaving no residue. Crystallized samples of commercial aconitia are the purest. Amorphous aconitia, and particularly that prepared in Germany, is very impure, being admixed with considerable quantities of comparatively inert bases. The use of such a preparation should be avoided, as being liable to give rise to a false idea as to the proper dose of the pure alkaloid (Royle’s Mat. Med., 1876, p. 773). Morson’s “English aconitine” (pseudaconitia) is much more powerful than the French and German products, which are mostly prepared from A. napellus, and consist mainly of aconitia.[221]

Aconitia and pseudaconitia differ from one another in their molecular weights and melting-points; they also furnish different decomposition-products: aconitia readily furnishes well-crystallized salts, while the salts of pseudaconitia are usually obtained amorphous; and finally, crystallized aconitia is anhydrous, while pseudaconitia crystallizes with one atom of water.

The two bases are similar as regards their physiological action (pseudaconitia is perhaps somewhat more powerfully active than aconitia), and general behaviour with reagents.

The characters and physiological action of commercial aconitia vary greatly, as might be expected from the ununiformity of its composition.

SEPARATION AND TESTS.

For the extraction and separation of aconitia from anima matters, the modification of Stas’s general method, described on page 5 (Chap. I.), may be employed. The alkaloids of aconite being, as has been already shown, very liable to decomposition, great care must be taken, during the extraction with alcohol and subsequent evaporation of the extracts, that the temperature does not rise above 50° C.: the use of mineral acids should also be avoided.

Tests.—1. The residue of aconitia or pseudaconitia, obtained on spontaneous evaporation of the anhydrous chloroform solution, will generally be found to be more or less crystalline, when examined under the microscope.

2. The Taste Test.—A minute portion of the residue, either alone or dissolved in a small quantity of water acidulated with acetic acid, should be rubbed with the finger on the lips and gums, or cautiously applied to the tip of the tongue. If aconitia or pseudaconitia be present, a peculiar tingling and numbness will be quickly experienced in and around the parts to which the alkaloidal extract has been applied: salivation, with a desire to expectorate, and a sense of swelling at the back of the throat, are also frequently noticed. The effects, or some of them, usually last from three to six hours, or even longer. This action is peculiar to aconite; the test, therefore, is of the utmost value, and one which must never be omitted.

3. The Physiological Test.—Inject a small quantity of the alkaloidal extract, dissolved in a little water acidulated with acetic acid, into the back of a mouse or other small animal. In the event of aconitia being present, characteristic symptoms of aconite poisoning are manifested in a few minutes, and the death of the animal rapidly ensues. Among the chief symptoms observed by Dr. Fleming, in some experiments upon animals, made in 1844, were “weakness of the limbs, staggering, a gradually increasing paralysis of the voluntary muscles, loss or diminution of sight, slowness of pulse, difficulty of breathing, occasional convulsive movements, in two cases opisthotonos, contracted pupils, but often dilating two or three minutes before death, and death by asphyxia.” (Woodman and Tidy’s For. Med., p. 394). This test is also a very important one.

4. Chemical Tests.—Solutions of salts of aconitia and pseudaconitia are precipitated by most of the general reagents for alkaloids, such as Mayer’s reagent, tannic acid, potassium tri-iodide, phosphomolybdic acid, &c. Platinic chloride, picric or carbazotic acid, and auric chloride, however, do not give precipitates, except in concentrated solutions. Among the special tests for aconitia and pseudaconitia which have been described, the following may be mentioned. (A) With sulphuric acid, no change takes place in the cold, but on warming, a pale yellow, deepening into brown, and finally changing into violet-red, is observed. This reaction varies very greatly with different samples of aconitia, and little or no reliance can be placed upon it as a toxicological test. (B) With sulphuric acid and a drop of saturated solution of sugar, a fine rose-red colour, passing into dingy brown, has been obtained. Experience, however, has not shown this test to be of any especial value. (C) If cautiously heated for ten or fifteen minutes on the water-bath with a few drops of syrupy phosphoric acid, aconitia is said to yield a violet or blue colour. This reaction is uncertain and therefore useless: it may be obtained with impure samples, while pure aconitia and pseudaconitia fail to give it. Mr. T. B. Groves (Year-Book of Pharmacy, 1873) says:—“The colour reactions of these alkaloids may be dismissed in a word. There are ‘none.’ As for the phosphoric acid reaction producing a blue colour, I have never succeeded in obtaining it. It is probably due to some accidental impurity, and I believe Dr. FlÜckiger has arrived at the same conclusion.”

Hence, as there are no reliable, characteristic, and distinctive chemical tests for aconitia, its presence or absence must be judged chiefly from the results of the tests of taste and physiological action on small animals. A substance, previously proved to be an alkaloid by its yielding precipitates with most of the general reagents for alkaloids, and which, when applied to the tongue and injected under the skin of a small animal, produces the effects already described, is absolutely certain to be aconitia.

HISTORY, PREPARATIONS, AND DOSES.

History.—The ?????t?? of the Greeks and Aconitum of the Romans are believed to refer to the genus Aconitum, if not actually to A. napellus. The ancients were well acquainted with the poisonous properties of aconite, which has been widely used as an arrow-poison. It was employed by the ancient Chinese, and is still in requisition among the less civilised hill tribes of India.[222] Something similar was in use among the aborigines of ancient Gaul. In a Welsh MS. of the 13th century, aconite was pointed out as one of the plants which every physician was to grow. The root and the herb are met with in the German pharmaceutical tariff of the 17th century. StÖrck, of Vienna, introduced aconite into regular practice about the year 1762 (FlÜckiger and Hanbury; “Pharmacographia,” 1879).

Preparations and Medicinal Doses,—Aconite leaves (Aconiti Folia) and root (Aconiti Radix) are officinal in the British Pharmacopoeia, and the plants from which they are obtained (A. napellus) are cultivated in Britain (Squire’s Companion to the B. P., 1868). The chief preparations are as follows:—

1. Aconitia, B. P.—Aconitine. Not for internal use, according to the Pharmacopoeia. It is, however, occasionally prescribed in very minute doses (¹/₄₀₀ to ¹/₅₀ of a grain by the mouth: not more than ¹/₂₀₀ of a grain, subcutaneously injected; Royle’s Materia Medica). Dr. J. Harley has given ¹/₂₀₀ of a grain, once a day, in fevers.

2. Unguentum AconitiÆ, B. P.—Ointment of aconitia. Prepared with lard. Strength, 8 grains of aconitia to the ounce (= 1·66 per cent.). For external application in painful nervous affections, neuralgia, &c.

3. Linimentum Aconiti, B. P.—Useful for external application in neuralgia or lumbago. May contain about 2 per cent. of aconitia (Blyth).

4. Extractum Aconiti, B. P.—Prepared from the leaves and flowering tops. Dose, 1 to 2 grains.

5. Tinctura Aconiti, B. P.—Dose, 5 to 10 minims, twice or thrice a day (Squire); 5 to 15 minims, and only to be gradually if at all increased (Royle); never to exceed 5 minims (Farquharson’s Therapeutics).[223]

6. Fleming’s Tincture of Aconite is not officinal; it is nearly four times stronger than the B. P. tincture, and must on no account be given in the above doses (Royle).

7. Liston’s Strong Tincture.—Not officinal.

8. Aconiti Succus.—The expressed juice. Not officinal. Dose, 15 to 20 minims (Squire’s Comp. to the B. P.).

9. Extractum Aconiti Rad.—Not officinal. Prepared with alcohol. Dose, half a grain.

Fatal Dose of Aconitia.—Smallest: in one case ¹/₅₀ of a grain nearly proved fatal (Pereira). The tenth and even twentieth of a grain are believed to have caused death (Headland; Herapath). The average quantity for an adult is probably between ¹/₁₆ and ¹/₂₀ of a grain. One drachm of the root, four grains of the alcoholic extract, and one drachm of the tincture have proved fatal.[224] Numerous well-authenticated cases are on record of aconite root being scraped and eaten at table, in mistake for horseradish, with very serious and even fatal results.[225] (See Guy and Ferrier’s For. Med., p. 617.)

Fatal Period.—The shortest time in which death has been known to occur is 1¼ hour: the longest, 20 hours: average, less than 4 hours (Guy and Ferrier). A case is mentioned in Woodman and Tidy’s Forensic Medicine, however, in which death occurred in 20 minutes. “The symptoms usually make their appearance in from a few minutes to one or two hours; whilst death usually takes place within three or four hours” (W. and T., p. 393).

PHYSIOLOGICAL EFFECTS.

Aconite produces, locally applied, a tingling sensation, followed by numbness, and the earliest symptom of poisoning by aconite, when any one of its preparations has been taken by the mouth, is tingling, followed by numbness and anÆsthesia of the lips and throat, afterwards becoming general. Vomiting occurs frequently, but not universally: purging is not nearly so frequent (W. and T.). The intellectual faculties are usually unaffected, but in some cases there is stupor. Aconite paralyses both the reflex and motor activity of the spinal cord, hence there is an almost total loss of muscular power. The respiratory centre is eventually paralysed, so that death may result from suffocation (Farquharson). The heart’s action becomes feeble and irregular; its rapidity is first diminished, then increased. The face is pale, and the body bathed in a clammy sweat: the pupils “are at first contracted, and afterwards dilated shortly before death.” The respiration becomes slower, then irregular, and death generally results from its cessation (asphyxia).

In cases of poisoning by aconite, death may be caused by (1) asphyxia, (2) shock, or (3) syncope.

The following symptoms were noted in the case of a cat, to which one-tenth of a grain of Morson’s English aconitia (= pseudaconitia, or nepaline) was administered:—stertorous and difficult breathing, staggering motions, convulsions (always contracting, never stretching like strychnia), vomiting, foaming at the mouth, moans and spasmodic cries, violent struggles for breath; the body fell over on one side, the limbs were stretched forward and worked spasmodically, but never stiffened. Attacks intermittent, with peaceful intervals. Involuntary defecation; retching (the stomach had already emptied itself), prolonged low moans, gasps for breath, abdominal rumblings, insensibility for two hours with occasional twitching, moans and cries. Eyes wide open, pupils not contracted. Finally, after 2½ hours, a few slight struggles, a convulsive gasp, and death. Stiffening very slow. Tongue protruded beyond the teeth.

Twelve hours after death, the rigidity was very strong. A post-mortem examination was then made, with the following results. Pupils dilated. Intestines and other organs normal, not congested: lungs collapsed and congested: heart very much venously congested. Blood not more fluid than usual. Larynx filled with frothy mucus. Brain congested.

On analysis of the stomach and other organs an alkaloidal extract was obtained, which, when submitted to the taste test, produced all the effects characteristic of aconitia. It is worthy of remark that the colour-tests completely failed.

Treatment and antidotes.—“Emetics, stimulants internal and external” (Squire’s Comp. B. P.). No chemical antidote is known: animal charcoal has been recommended, but its efficacy is doubtful. A mustard emetic should be applied, followed by the stomach-pump. “In the latter stages, depletion from a jugular vein to relieve the distension of the right heart, accompanied by the most persevering efforts to promote the expansion of the chest.” Gentle magneto-electric currents down the back of the neck and around the margin of the ribs, to excite contractions of the diaphragm, accompanied by rhythmical abductions of the upper extremities, should be employed. If there is yet a capability of swallowing, brandy and ammonia should be given (Royle’s Mat. Med.).

Remarks.

Pure aconitia is perhaps the most deadly poison with which we are at present acquainted, and all the preparations of aconite are excessively poisonous. Unless employed with extreme caution they are very dangerous, and should on no account be used, even for external application, except with the advice of, or by a medical man.[226]

The urgent necessity for an alteration in the law at present relating to the sale of poisons, and for the introduction of a clause placing some restrictions on the sale of patent medicines containing poisons, is strikingly shown by the fact that such preparations as “Neuraline” are now sold without any restriction whatever. Indeed, as the law at present stands, the most virulent poisons, if contained in, or sold as patent medicines, can be obtained by any ordinary person with less difficulty than the same poisons can be purchased, under their own proper names, by a medical man. Neuraline, a patent medicine containing a preparation of aconite, was brought rather prominently forward, in 1872, in connection with the death of the Hon. G. C. Vernon, the question arising as to whether the too frequent use of neuraline by the deceased, for pains in his head, had been the cause of death.[227]

The phosphoric acid test for aconitia, referred to by Mr. Montagu Williams during the trial of Dr. Lamson, is described in Professor FlÜckiger’s work (“Pharmaceutische Chemie”; Berlin, 1879); but it is at the same time mentioned that crystallized aconitia gives only an extremely faint reaction, and crystallized nitrate of aconitia none at all.

It has been already pointed out (p. 573) that this test is one which cannot be relied on, and that the violet colour is believed to be due to impurities present rather than to aconitia itself.

The internal administration of aconitia in very small doses is recommended, in cases of dysentery and typhoid fever, by a writer in the Journal of Medicine and Dosimetric Therapeutics, according to the method of Dr. Ad. Burggraeve, a publication edited by Dr. T. L. Phipson. Dr. Burggraeve’s method (or “dosimetry,” as it is called) is in several respects similar to homoeopathy, and the journal in question cannot be regarded as a generally accepted authority.

In his speech for the defence, Mr. Montagu Williams referred to the supposed existence of cadaveric alkaloids or ptomaines, and to the absence of special chemical tests for aconitia. With reference to the ptomaines, see Chap. 1, p. 12. The objection, that there is no characteristic chemical test for aconitia, is to a great extent deprived of its force when one remembers that aconitia can be proved to be an alkaloid by its deportment with the general alkaloidal re-agents; that the taste test alone will distinguish it from all other alkaloids; and that it exerts a powerful and distinctive action on small animals, and ultimately destroys them.

It must not be forgotten that the remark of Lord Coleridge’s, quoted by Mr. Montagu Williams, is nothing more than an expression of personal opinion, by an eminent lawyer on a purely scientific subject; valuable, no doubt, but not necessarily infallible.

The statement of Messrs. Allen & Hanbury’s assistant, that aconitia is yellowish-white (p. 544), does not hold good of all samples: the colour of the alkaloids varies with their degree of purity, and pure aconitia is not less white than pure atropia.

Full details of the case of poisoning by aconitia, referred to by Dr. Stevenson (p. 534), are to be found in Schmidt’s JahrbÜcher der In-und AuslÄndischen gesammten Medicin, edited by Dr. Adolf Winter, vol. 189, p. 122: the case was originally communicated by T. Haakma Tresling to a Dutch journal (Weekbl. van het Nederl. Tijdschr. voor Geneesk, 16, 1880). The following is a short account of this case.

A patient, for whom medicine containing aconitia nitrate (to be taken in small and repeated doses) had been prescribed by a physician, Dr. M., experienced soon after the first and second doses a burning sensation in the throat, followed by vomiting and, later on, by difficulty of respiration: the skin was icy cold to the touch, although internally there was a sensation of burning throughout the body. With the object of proving that these effects were not attributable to the medicine, Dr. M., at four p.m. on March 16th, 1880, took a dose of the mixture, containing rather more than ¹/₁₆ grain of aconitia nitrate. The first symptoms of poisoning appeared in about an hour and a half; and, about four hours after he had taken the poison, Dr. M. was found to be pallid, with a cold skin, contracted pupils, small and irregular but not accelerated pulse, swollen tongue, headache, shivering fits, and a sensation of burning in the mouth: there was also pain extending from the throat to the lower part of the stomach. Suddenly the power of vision became extinct, simultaneously with a great dilation of the pupils: sight shortly afterwards returned, the pupils at the same time again contracting. Vomiting was induced by tickling the throat; the ejected matter was thick, red-coloured, and contained the remains of food previously consumed: vomiting subsequently recurred spontaneously. The first convulsions occurred eight hours and forty minutes after the dose had been taken; respiration became more difficult, and Dr. M. complained of humming in the ears, and deafness, first in one ear and then in the other. Ether was now subcutaneously injected: dilation of pupils, with loss of vision, again followed, being succeeded by vomiting, and violent and long-continued convulsions. In eight hours and fifty-three minutes extraordinarily violent vomiting set in, and was followed by a succession of violent convulsions. Dr. M. could not again be restored to consciousness, the pupils were dilated and remained unaffected by the light, and respiration was slow and laborious. Notwithstanding the employment of electricity, breathing became slower, the beating of the heart ceased to be audible, and death occurred in nine hours from the time at which the poison was taken.

On a post-mortem examination being made, it was found that the surface-tissues of the body were very pale and contained little blood, while the internal organs were much congested. The intestinal congestion increased towards the stomach, and diminished towards the large intestine. The colon, rectum, and bladder were very pale and bloodless. The latter contained about 70 grammes (= 2¼ fl. oz.) of urine. The liver and spleen were enlarged, the kidneys small; all much congested. Defecation had not taken place, though some urine had been passed. The lungs did not fill the cavity of the chest; they contained fresh infiltrations and some small cavities: adhesion, congestion, and, in the lower portions, numerous emphysematous patches. Much fat was deposited on the right side of the heart, which contained thin blood. Brain congested.