Aconitum. U. S. (Br.) Aconite.
Aconit. [Monkshood, Aconite Root, Aconiti tuber P. I.]
"The dried tuberous roots of Aconitum Napellus Linne (Fam. Ranunculaceae), without the presence or admixture of more than 5 per cent. of stems or other foreign matter, and yielding not less than 0.5 per cent. of the ether-soluble alkaloids of Aconite. If made into a fluidextract and assayed biologically the minimum lethal dose should not be greater than 0.00004 mil for each gramme of body weight of guinea-pig." U. S. "Aconite Root is the dried root of Aconitum Napellus, Linn." Br.
Aconiti Radix, Br.; Aconite Root, Monkshood, Wolfs-bane, Wolfroot, Friar's cap, Cuckoo's cap, Blue rocket; Racine d'Aconite, Aconit, Coqueluchon, Aconit Napel, Fr.; Tubera Aconiti, P. G.; Eisenhut, Eisenhutknollen, Sturmhut, Mönchskappe, Akonitknollen, G.; Aconite, It., Sp.
The name Aconite is derived, according to Pliny, from the Black Sea port, Acone. While the drug was used by the ancient Chinese as well as by the hill tribes of India, it was introduced into modern medicine by Storck, of Vienna, in 1763. The genus Aconitum is a relatively large one, there being some sixty well-defined species, nearly half of which have been used in medicine. The species which is official and recognized by nearly all the Pharmacopoeias is Aconitum Napellus. It is indigenous to the mountainous regions of Middle Europe and is found growing in Northern Europe, Siberia and Central Asia. It is extensively cultivated in temperate climates for its foliage and flowers and has been successfully grown in the testing garden of the U. S. Department of Agriculture. Schneider reports that it has become naturalized to some extent in California. There are five species of Aconitum which are indigenous to the mountainous regions of the Northern United States, two of these being found in the Rocky Mountains and on the Pacific Coast. Holm describes the morphology and structural characteristics of the wild Monkshood of the United States, A. uncinatum L., in Merck's Rep., 1907, p. 65.
The roots or rhizomes of several other species of Aconitum are found in commerce, these being chiefly used in the manufacture of the alkaloids.
(1) The tuberous roots of A. variegatum L. and of A. Stoerkianum Reich, are sometimes found in the commercial drug. These are smaller, not so pungent, although quite active.
(2) Japanese Aconite is derived from A. Fischeri Reich and A. japonicum Thunberg. The roots are light gray in color, fleshy, being smaller than the official tubers. They have a circular cambium and the starch grains are more than 0.015 mm. in diameter. They are largely imported into Europe and to some extent. to this country.
(3) Indian Aconite is derived from A. ferox Wall., a plant growing in the Himalayas and in Nepal. The roots are from 5 to 10 cm. long and from 2 to 4 cm. in diameter, being externally grayish-brown and deeply furrowed. They are hard, the fracture being either horny or mealy and the inner surface is either yellowish-brown or whitish. The cambium is 7- to 9-rayed and the taste resembles that of the official Aconite.
(4) Another species of Aconitum that is very poisonous is A. Lycoctonum L., of Europe and Northern Asia. This, however, does not produce a tuberous root, but develops an oblique rhizome surrounded with numerous roots.
5) The fleshy roots of A. heterophyllum Wallich., a plant growing in the West Himalayas, are somewhat ovoid and flattened at the summit and base. Externally they are grayish-brown. The odor resembles that of black pepper and the taste is bitter and acrid. The rhizome contains an amorphous bitter alkaloid, atisine, which is not toxic. Under the name of Utees, Atees, or Atis, the rhizome and roots of A. heterophyllum are said to be largely employed in doses of 20 grains as an antiperiodic. Wakhma is the root of A. palmatum Don, in which Jowett found aconitic acid and the alkaloid atisine, C22H33NO3, which, according to Cash, is physiologically very feeble. (J. Chem. S., 1896.)
Aconitum Napellus is a perennial herbaceous plant, with a conical-shaped, tapering root, seldom exceeding 10 cm. in length and 2 cm. in thickness near the summit, brownish externally, whitish and fleshy within, and sending forth numerous long, thick, fleshy rootlets. When the plant is in full growth, there are usually two roots joined together, of which the older is dark brown and supports the stem, while the younger is of a light yellowish-brown, and is destined to furnish the stem of the following year, the old root decaying. The stem is erect, round, smooth, leafy, usually simple, and from two to six or even eight feet high. The leaves are alternate, petiolate, divided almost to the base, from two to four inches in diameter, deep green upon their upper surface, light green beneath, somewhat rigid, and more or less smooth and shining on both sides. Those on the lower part of the stem have long footstalks and five or seven divisions; the upper, short footstalks and three or five divisions. The divisions are wedge-form, with two or three lobes, which extend nearly or quite to the middle. The lobes are cleft or toothed, and the lacinise or teeth are linear or linear-lanceolate and pointed. The flowers are of a dark violet-blue color, large and beautiful, and are borne at the summit of the stem upon a thick, simple, straight, erect, spike-like raceme, beneath which, in the cultivated plant, several smaller racemes arise from the axils of the upper leaves. Though without calyx, they have two small calycinal stipules, situated on the peduncle within a few millimeters of the flower. The petals are five, the upper helmet-shaped and beaked, nearly hemispherical, open or closed, the two lateral roundish and internally hairy, the two lower oblong-oval. They enclose two pediceled nectaries, of which the spur is capitate, and the lip bifid and revolute. The fruit consists of three, four, or five follicles. The seeds are wrinkled or scaly and very acrid.
The plant is abundant in the mountain forests of France, Switzerland, and Germany. It is also cultivated in the gardens of Europe, and has been introduced into this country as an ornamental flower. All parts of the plant are acrid and poisonous. The leaves and root are used. The leaves should be collected when the flowers begin to appear, or shortly before. After the fruit has formed, they are less efficacious. The fresh leaves have a faint narcotic odor, most sensible when they are rubbed. Their taste is at first bitterish and herbaceous, afterwards burning and acrid, with a feeling of numbness and tingling on the inside of the lips, tongue, and fauces, which is very durable, lasting sometimes many hours. When long chewed, they inflame the tongue. The dried leaves have a similar taste, but the acrid impression commences later. Their sensible properties and medicinal activity are impaired by long keeping. They should be of a green color, and free from mustiness. The root is much more active than the leaves, and an extract from the latter is said to have only one-twentieth of the strength of one made from the former. It should be gathered in autumn or winter after the leaves have fallen, and is not perfect until the second year. It has been mistakenly substituted for horseradish root, as a condiment, with fatal effect. The wild plant is said to be more active than the cultivated. (Schroff.) Procter found the roots of the plant cultivated in this country richer in active alkaloidal principles than the imported roots, having obtained as much as 0.85 per cent. from the former. (Proc. A. Ph. A., 1860.) The studies of P. W. Squire seem to show that in the autumn the root is the most active. So far, however, as concerns the whole plant, the practical difficulty is that the root of A. paniculatum Lam. cannot be distinguished from that of A. Napellus, except by taste; so that the custom which seems to prevail of gathering the root about the flowering period is probably well founded. The plant is being cultivated to some extent for medicinal purposes in England, but much of the stock is of doubtful nature, owing to the extraordinary tendency of A. Napellus to hybridize with other species and to alter under cultivation. (See P. J., 1889, 645.) For Keller's test for aconite root and leaves, see Proc. A. Ph. A., 1895, 539.
Aconite root is generally brought into market in packages or bales, either from the continent of Europe or from India. It is of variable quality, some parcels being unobjectionable, while others contain a considerable proportion of inert or defective roots. Among these roots that of Imperatoria Peucedanum Ostruthium has been especially observed. (P. J., vii, 749.) The best test is the taste; roots should be rejected which have not in a fair degree the characteristic properties in this respect described below, especially the production of the sensation of numbness and tingling on the tongue, lips, and fauces. One shipment of aconite consisted entirely of Japanese aconite. The powdered drug is sometimes adulterated with the endocarp of the olive or so-called "olive pits." The latter is not easily detected, as aconite contains a large number of stone cells. The latter, however, have relatively thin walls and the various forms have been described by Stingel in A. J. P., 1913, p. 391.
Nepaul aconite, known in India as "Bikh" or "Bish" aconite, is supposed to be derived from A. spicatum or A. laciniatum. There is a question about this as the Nepaul aconite of European commerce yields the alkaloid pseudaconitine and this principle is only present in the roots of A. deinorrhizum and A. Balfourii. (Bulletin of the Imperial Institute, 1906, p. 32.) Nepaul aconite is composed of elongated fusiform or nearly cylindrical roots which are more or less flattened, longitudinally furrowed and from 7.5 to 10 cm. in length.
Properties.—The German Pharmacopoeia restricts aconite to the bud-crowned tubers of wild growing plants. Most of the other Pharmacopoeias permit the use of stem-crowned roots. In the former case the daughter tubers terminated by their buds are employed, whereas in the latter the older tubers which have developed foliage and flower stems are used. The commercial drug shows considerable variation and is usually a mixture of six or seven different kinds of tubers, as follows:
- Single fleshy tubers which are smooth, light brown and full of starch.
- Single tubers which are single, somewhat elongated fusiform, crowned with short stems, dark brown and longitudinally furrowed.
- Twin tubers, one of which is bud-crowned and the other having a short stem at the summit.
- Very small single tubers usually crowned with stems, the lower portion being acute or pointed.
- Single tubers which are almost cylindrical, crowned with stems and either fleshy and nearly smooth or more or less shrunken and furrowed.
- Dark brown resinous tubers.
- And finally fragments of small and nearly filiform roots.
The root has a feeble earthy odor. Though sweetish at first, it has afterwards the same effect as the leaves upon the mouth and fauces. It shrinks much in drying, and becomes darker, but does not lose its acridity. Aconite root is officially described as being " more or less conical or fusiform, from 4 to 10 cm. in length and from 1 to 2 cm. in diameter at the crown; externally dark brown or grayish-brown, smooth or longitudinally wrinkled, the upper end with a bud, remains of bud-scales or stem-scars, the other portions with numerous root-scars or short rootlets; fracture short, horny or somewhat mealy; internally, bark light or dark brown, 1 to 2 mm. in thickness, cambium zone usually 5- to 8-angled, with a small fibrovascular bundle in each angle, pith whitish or light brown, from 2 to 7 mm. in diameter; odor very slight; taste sweetish, soon becoming acrid and developing a tingling sensation, followed by numbness. Under the microscope transverse sections, made near the middle of the tuberous root of Aconite, show an outer layer consisting of one or more rows of cells with blackish-brown walls; a primary cortex of 8 to 15 rows of parenchymatous cells and interspersed with characteristic stone cells, which occur either singly or in small groups; a more or less modified endodermis; a secondary cortex, consisting chiefly of starch-bearing parenchyma and interspersed with a few small fibrovascular bundles; a more or less star-shaped and characteristic cambium with from 5 to 12 collateral fibro-vascular bundles; and a pith composed of large, starch-bearing parenchyma cells. The powder is grayish-brown; starch grains numerous, spherical, somewhat plano-convex, single or 2- to 5-com-pound, the individual grains from 0.003 to 0.015 mm. in diameter and frequently with a central cleft; trachea? mostly with slit-like, simple pores, sometimes with spiral or reticulate thickenings or with bordered pores; stone cells single, tabular, irregular in shape or elongated to fibers, from 0.1 to 0.4 mm. in length, walls from 0.008 to 0.025 mm. in thickness, strongly lignified and having large, simple pores; fragments of cork few, yellowish-brown; fragments of parenchyma numerous, the cells being filled with starch grains; bast-fibers from stems few, very long, with lignified walls about 0.005 mm. in thickness, and marked by transverse or oblique, slit-like pores. Aconite yields not more than 6 per cent. of ash." U. S.
The following standards for aconite root are given in the British Pharmacopoeia: "From four to ten centimetres long, and from one to two centimetres wide at the upper extremity. Conical, dark brown, with numerous root scars, and crowned with base of the stem or the remains of a bud. Internally solid and starchy. In transverse section a stellate cambium with small vascular bundles at the projecting angles; primary cortex narrow, with isolated thick-walled sclerenchymatous cells; cells of parenchymatous tissue contain numerous small simple or compound starch grains. No marked odor; taste at first slight, followed by persistent sensation of tingling and numbness." Br.
The British Pharmacopoeia formerly recognized the flowering tops of the Aconite (Aconiti Folia). To be effective they should be collected just as the flowers are beginning to expand, at which time they are richest in alkaloid. The dried leaves are stated to contain about 0.3 per cent. and the flower-buds about 0.4 per cent. of aconitine. In the absence of any reliable chemical tests for aconitine E. R. Squibb suggested that a fluidrachm of a highly diluted solution of the various preparations be taken into the anterior part of the mouth (after the latter has been thoroughly rinsed) and held there for one minute exactly, and then discharged. The peculiar numbing sensation should be experienced within fifteen minutes, and it should continue for fifteen or thirty minutes. Tested in this way, he found the commercial aconitines, in solution of the strength of 1/900 grain in 1 fluidrachm of water, to have the following relative strengths; 1 grain of good powdered aconite root is equal to 1 grain of ordinary commercial aconitine, ⅛ grain of Merck's ordinary aconitine, 1/29 grain of Merck's pseudaconitine, 1/111 grain of Duquesne's crystallized aconitine (really aconitine nitrate). He also found by this approximate method that 1 grain of powdered aconite root was equivalent to 1.5 minims of Fleming's tincture, 9 grains of powdered aconite leaf, 1.5 grains of alcoholic extract of dried aconite leaf, 1 grain of Alien's English extract of fresh plant, and 72 minims of tincture of aconite leaf. For methods of assaying aconite, reader is referred to A. B. L. Dohme's paper (Proc. A. Ph. A., 1895, 206); also P. J., 1895, 860; D. C., 1900, 69, 132.
Assay.—The quality of aconite root is officially determined by an assay as follows: " Proceed as directed under Belladonna Radix, using 15 Gm. of Aconite in No. 40 powder and ether only as the immiscible solvent throughout the assay. Each mil of tenth-normal sulphuric acid V.S. consumed corresponds to 64.539 milligrammes of ether-soluble alkaloids of Aconite." U.S.
"Yields not less than 0.40 per cent. of ether-soluble alkaloids when assayed by the following process: Into a small stoppered glass percolator, provided with a glass tap and suitably plugged with cotton wool, introduce 10 grammes of Aconite Root in No. 40 powder and 75 millilitres of alcohol (70 per cent.). Macerate for four hours, shaking occasionally. Then allow percolation to proceed slowly until the liquid ceases to drop. Continue the percolation by the addition of more of the same menstruum until 150 millilitres have been collected or the Root is exhausted. Evaporate the percolate to dryness in a .shallow porcelain evaporating basin, at a temperature not exceeding 60° C. (140° F.). Dissolve the residue in 5 millilitres of N/10 solution of sulphuric acid diluted with 20 millilitres of water. Filter into a separating funnel, washing the dish and filter with about 30 millilitres of water. Add to the mixed filtrate and washings 25 millilitres of ether and 2 millilitres of solution of ammonia, and shake for one minute. After separation draw off the lower layer into a flask, and filter the ethereal solution into a beaker. Return the contents of the flask to the separator, add 20 millilitres of ether and again shake for one minute, separating the aqueous liquid and filtering the ethereal solution into the beaker. Repeat the operation with two other portions, each of 20 millilitres, of ether. Evaporate the mixed ethereal solutions to dryness, dry the residue at 60° C. (140° F.), dissolve it in 5 millilitres of N/20 solution of sulphuric acid diluted with 20 millilitres of water, and titrate back with N/20 solution of sodium hydroxide, tincture of cochineal being used as indicator. Deduct the number of millilitres of the alkaline solution required from 5, multiply the difference by 0.3217; the result will be the percentage of ether-soluble alkaloids in the powdered Root." Br.
Biologic Assay.—Because of the great variation in the activity of the various alkaloids of aconite a chemical assay does not offer an accurate criterion of the activity of a sample of this drug", and the Pharmacopoeia has very properly, therefore, permitted a standard of toxicity. As the different alkaloids resemble each other very closely in the type of their effect varying only in degree, it is not necessary to standardize the drug for any one physiological effect, and, as the sharpest physiological end reaction is death, the best test for the activity of a. specimen of aconite is determination of its lethal dose. The test recommended by the Revision Committee for aconite is based upon the determination of the minimum lethal dose for guinea-pigs.
"The guinea-pigs to be utilized should be of average size and not too large; preferably from 250 to 350 Gm. in weight and in healthy condition. The drug may be administered in the form of fluidextract, extract, or tincture, which in the preliminary trial may be injected subcutaneously into a series of guinea-pigs in doses having sufficiently wide limits. If the extract is to be standardized, it must be dissolved in sufficient solvent to produce a liquid preparation before injection. The animals after injection are placed in cages and at the end of the observation (twelve hours), note is taken of those living and dead. After this preliminary test, the limits of the doses for a second series of animals are further narrowed and, if necessary to still further confirm the earlier results, additional series may be injected until the minimum lethal dose for the guinea-pig is found.
"Standard.—A satisfactory preparation of the Fluidextract of Aconite should kill guinea-pigs when administered in doses of 0.00004 mil for each gramme of body weight of guinea-pig; a satisfactory Tincture of Aconite should prove fatal to guinea-pigs when given in doses of 0.0004 mil for each gramme of body weight of guinea-pig and a satisfactory Extract of Aconite should have a minimum lethal dose not greater than 0.00001 Gm. for each gramme of body weight of guinea-pig." U. S.
It is well to take a series of four guinea-pigs, each of which will be injected respectively with 0.03, 0.04, 0.045, and 0.05 milligramme for each gramme of body weight. If none of the animals survive the drug is too strong, if none of them die it is too weak. If some survive and some die it is necessary to test the drug on a second series in which case the test should be 0.038, 0.04, 0.042 milligramme; it is well to have at least two animals who receive the middle dose of these three. If the drug be of official quality those who receive 0.038 should survive, those which receive 0.042 should die, and of those which receive 0.04 some should die and some survive. In testing the crude drug-it may be made up conveniently in the form of a fluidextract and diluted with nine volumes of water. The syringe used must be standardized and graduated in tenths of a mil. The injection should be made subcutaneously, preferably beneath the skin of the abdomen. After the injection the animals are marked or placed in separate cages and at the end of 12 hours notice taken of those living or dead.
Uses.—Aconite was well known to the ancients as a powerful poison, but was first employed as a medicine by Baron Storck, of Vienna, whose experiments were published in the year 1762.
Locally aconite is actively irritant and also a paralyzant to the peripheral sensory nerves. When applied to a mucous surface it produces at first a burning tingling sensation followed in a few minutes by a numbness. This sensation may even be perceptible after the systemic ingestion of very large doses. When administered internally the most marked changes are seen in the circulation. The first effect is generally a slowing of the pulse, due to stimulation of the cardie-inhibitory centers, with consequent fall in the blood pressure. After somewhat larger doses, however, there is a weakening of the force as well as reduction of the rate of the pulse brought about by a direct action on the heart muscle. After poisonous doses various irregularities of heart action are produced and often there will be complete lack of harmony between the contraction of the auricle and ventricle. After fatal doses the heart is arrested in complete diastole and will respond to neither electrical nor mechanical irritation. In the frog, large quantities of aconite produce a loss of reflex activity, which is apparently due to a paralysis of sensation as voluntary motion is preserved for some time later, although it too may eventually be abolished. The drug appears to affect both the sensory nerves and the receptive side of the spinal cord, although the latter is involved comparatively late in the poisoning. In mammals this depressant action upon the nervous system can scarcely be demonstrated because of the powerful depressant effect upon the circulation.
Aconite is used chiefly as a circulatory sedative in conditions attended with excessive action of the heart or high arterial tension. Thus in valvular lesions of the heart in which the muscle tone is good, but the heart is over acting, in the so-called irritable heart seen in improperly trained athletes and similar conditions, it is often a remedy of great service. The choice between aconite and digitalis in such cases will depend largely upon the condition of the heart muscle; when the latter is strong and of good tone aconite may be used, but if there be a tendency towards dilatation, digitalis is generally preferred. In chronic high blood pressure, by retarding the pulse rate it will often produce a sensible reduction in the tension but in acute hypertension or threatened apoplexy it is less certain in its effects than the nitrites, but may at times be advantageously combined with them, By virtue of the lowering of the blood pressure aconite tends to increase the sweat and is frequently used as a sudorific, especially in febrile conditions. In sthenic fevers its effect in restraining the heart as well as its diaphoretic tendency often renders it a drug of much use.
Aconite is also frequently employed for its local effects. The combination of local irritant effects with anesthetic action suggests strongly its use in peripheral neuralgias. It must not be forgotten, however, that if used too freely for this purpose it may be absorbed through the skin in sufficient quantities to cause serious poisoning. It is also occasionally employed as a local anesthetic to the stomach in various types of vomiting or gastralgia, but on account of its systemic effect is practically of secondary value.
For internal use the best preparation is the tincture which may be given in doses of from five to fifteen minims (0.3-0.9 mil). For external application the fluidextract may be employed, but generally an ointment is preferred. This may be made by rubbing up the extract with two or three parts of lard, or the ointment of aconitine of the British Pharmacopoeia may be used. The U. S., 1870, recognized a plaster of aconite.
Toxicology.—Aconite is a rapidly acting and powerful poison. The symptoms produced by overdose of it are sensations of warmth in the stomach sometimes with nausea but usually without vomiting, with slowing of the pulse and of the respiration, the skin is cool and moist and there is profound prostration. As the poisoning-progresses the respirations become more slow and shallow, the pulse more and more feeble and towards the end may become rapid or very irregular. A characteristic symptom, in fact the only symptom of diagnostic importance, is the peculiar numbness and tingling first felt in the lips and mouth, but later also often in the fingers. At times there is dimness of vision, the pupils may be either contracted or dilated and occasionally delirium and stupor or convulsions may precede the fatal termination.
In the treatment of aconite poisoning the patient should be kept absolutely in a horizontal position or with the feet higher than the head. For the purpose of emptying the stomach the stomach pump is preferable to emetics as the latter involve a more or less serious strain upon circulation. Circulatory, stimulants, such as strychnine, ammonia, and atropine, may be given hypodermically. Body temperature should be maintained by external application of heat.
Dose, of aconite root, one-half to one grain (0.032-0.065 Gm.).