The bark of Alstonia constricta, F. Mueller.
COMMON NAMES: Native quinine of Australia, Australian fever bark, Fever bark, Bitter bark, Alstonia bark.
Botanical Source.—The genus Alstonia comprises about twelve species, seven of them being given in Bentham's Flora of Australia. They are milk bearing shrubs or trees, with large, entire, generally whorled leaves, and terminal cymes of white flowers. Alstonia constricta, F. Mueller, is a lactescent, smooth tree, found growing only in Australia, and has large, opposite, entire oblong leaves about 4 inches long, borne on slender leaf-stalks. The flowers are small, white, numerous, and disposed in corymbose cymes. The calyx is deeply 5-parted and has ovate acute lobes. The corolla has a bell-shaped tube, about twice the length of the calyx, and 5 equal spreading lobes. The stamens are 5, distinct and included. The pistil consists of 2 carpels, with a single style. The fruit consists of a pair of slender, smooth pods, from 3 to 8 inches in length, and containing numerous, flat, pubescent seeds, the upper margins of which are fringed with long hairs.
Description, Chemical Composition, and History.—The bark is used in Australia as an antiperiodic. As found in commerce, it is in pieces varying in length from 6 inches to 2 feet, from ½ inch to 3 inches in thickness, and from 2 to 4 inches in width. That from the young trees or branches is often curled, like cinnamon bark, until the edges meet, or even overlap. The accurate description given by Mr. Chas. Mohr in the Amer. Jour. Pharm., August, 1879. is as follows: "The bark occurs in semicircular pieces of various length, about 4 inches wide and from 1 ½ to 2 inches and over in thickness, according to the more or less exuberant development of the corky layers. The rough outer bark is furrowed by more or less broad and deep longitudinal fissures, presenting in the cross section a margin correspondingly, deeply indented by irregular, more or less wide and deep sinuosities. The exposed surface of the bark is of a dingy gray-brown, and of an ochre color where fresh layers of cork are exposed. This outer bark, forming far the largest part, shows in the cross section a mottled yellow and brownish color, resulting from somewhat irregular, concentric layers of a clear ochry-yellow, alternating with bands of a deeper tint. It is of spongy texture and friable. The middle and inner layers, about ¼ of an inch in thickness, are compact and homogeneous in the cross sections, of a yellow color, and under the lens appearing punctate from the darker faces of the bast-bundles; of a fibrous structure, hard and tough, and on the inner side serrated by longitudinal ridges, caused by the impressions of the bast-bundles upon the cambial layer. The powder of the bark is of a dingy yellow, and possesses a faint, not unpleasant odor, and a lasting, purely bitter taste. The active principles are contained chiefly in the middle and inner bark."
This bark is of a comparatively recent introduction, having been shown for the first time in this country at the Centennial Exposition, in the Australian department, where it was asserted by its exhibitors to be a remedy for malarial fevers. A Cincinnati gentleman, having had his attention strongly attracted toward these assertions, procured a specimen of the bark and, after investigation, having found it to possess therapeutical virtues, he ordered a supply from Australia, intending to introduce it as a proprietary medicine. Prof. J. M. Scudder, of Cincinnati, persuaded him, however, to give up his intention, and allow it to come before the medical profession under its true name, Alstonia constricta, the positive identification of which Mr. Charles Mohr effected through specimens sent by him to Sir Joseph Hooker.
The chemical constituents have been investigated repeatedly. Alstonine (chlorogenine of Hesse), is the name given in Wittstein's Organic Constituents of Plants, for an orange-yellow, amorphous alkaloid, isolated by Mueller and Rummel. Mohr (1879) found a substance agreeing with that of M. and R. in all respects, and announced the probable presence of another proximate constituent; but want of material prevented a thorough examination. Oberlin and Schlagdenhauffen (Pharm. Jour. and Trans., June, 1879, from "Jour. de Pharm. et de Chimie"). report an analysis of the bark, and the isolation of two alkaloids: One, alstonine, in crystalline tufts, bitter, colorless, soluble in alcohol, chloroform, and benzin; insoluble in cold, but somewhat in boiling water; soluble in nitric, hydrochloric and sulphuric acids, without color, but which neutralizes acids, changes red litmus paper to blue, and the acid solutions of which produce fluorescent (blue) liquids. The other, "alstonicine," is amorphous, and is obtained from the mother liquor after the production of alstonine. It somewhat resembles alstonine, but is not as soluble in boiling water, turns a red-crimson color with nitric, and greenish-brown with sulphuric and hydrochloric acids, and the acid solutions are not fluorescent. In 1880, Hesse established with certainty the presence of the following three alkaloids: Alstonine (C21H20N2O4), identical with his chlorogenine of 1865 and the alstonine of Palm (1863); orange-yellow, not easily soluble in water, easily soluble in alcohol, chloroform, ether and dilute acids, the solutions having blue fluorescence. Porphyrine (C21H25N3O2), is white and noncrystalline; dissolves in concentrated sulphuric acid with purple color, the acid solutions being fluorescent, with blue color. Alstonidine, less soluble in petroleum benzin than porphyrine. Hesse indicated the existence of other alkaloids besides those mentioned. All reports agree, however, that these proximate principles exist in very small amount. Doubtless, either the bark in substance, or the tincture, or the fluid extract, will be the medicinal preparations employed; the most effectual being prepared from the inner bark.
Von Mueller appears to have been the first person who made known the febrifuge properties of this bark, in 1870, in an address before the Industrial Museum of Melbourne; in 1874, in a published statement relative to certain select plants, he again remarks that the bark of A. constricta is aromatic, bitter, and regarded as valuable in ague; also as a general tonic. It was subsequently referred to as an antiperiodic, in 1876, by Dr. A. Cathcart, of South Wales. Its introduction to the materia medica of this country justly belongs to Prof. J. M. Scudder, M. D., of Cincinnati. It is said that English brewers substitute it for hops in the making of pale export beer, for, unlike the hops, it will not produce headache (Christy). A decoction of fever bark is sold in some of the English colonies as "bitters."
Action, Medical Uses, and Dosage.—The inner bark of Alstonia constricta is said to possess marked antiperiodic properties, while the outer bark is stated to have been efficacious in curing certain forms of rheumatism. Further trials are needed, however, before it can be ranked as a substitute for quinine, or other of the cinchona alkaloids, yet it has proved as efficient in intermittents. "Hesse attributes to alstonidine properties analogous at once to those of quinine and to nux vomica. The experiments of Bancroft and of Bixby prove that this drug is valuable as a tonic febrifuge, and more valuable as a febrifuge than as a tonic, while the Alstonia scholaris is more generally employed against dysentery" (Beringer, Amer. Jour. Pharm., 1895, p. 167).
Prof. King has used the bark in several cases with prompt and decided success; four of these cases were small children. The inner bark was given to the patients in a dose of from 4 to 8 grains, an hour or two before the expected chill, repeating the dose 2 or 3 times, each time anterior to the anticipated chill. Three doses were usually required; in one case, only 1 dose was given, and in two others, 4 doses were taken before the chills disappeared. The most marked influence was in an obstinate case, tertian, invariably attended during the attacks with gastric pain and irritability, and neuralgic pains in the superior extremities; the first dose afforded much relief, and since the third dose the patient has been entirely free from any symptoms of the malady, and has, for the first time in several years, passed an autumnal season without any chills, while neighbors were suffering more or less severely from them. Professor Locke has used it successfully in chronic intermittent, but thinks it not so efficacious in the acute forms. Prof. J. M. Scudder also had considerable success with it. He regarded it an excellent tonic and restorative when the secretions are depraved, the bowels irregular, tongue inclined to be dirty, skin dirty and sallow, and the urine depositing a sediment (Spec. Med., 69 (not in the 1870 edition)). Many physicians have reported favorably as regards its antiperiodic virtues, having successfully used it where quinine had failed. From the fact that it corrects depraved states of the blood in malarial disorders, Webster contends that it should not be termed an antiperiodic, but rather a corrective of malarial cachexia. Dr. John Fearn favors its use in chronic malarial poisoning, and gives as its specific indications: Tongue dirty, skin sallow, and urine turbid, with periodicity. Gastro-intestinal disorders, depending upon chronic malaria, such as lienteric diarrhoea, dysentery, and atonic dyspepsia, are reputed to be cured by it. According to Dr. R. E. Kunze, of New York City, this bark possesses slightly narcotic, cerebro-stimulant, antiperiodic, febrifuge, and tonic properties; he has used it with success in several cases of intermittent fever, though, from its peculiar effects in certain cases, he is rather inclined to consider its use contraindicated in "patients of a delicate and highly nervous organization." Among the patients with whom it has acted favorably, it not only checks the ague, but appears also to prevent its return, for the season, at least. The bark is very bitter, and produces different effects with different parties; among these effects may be named a persistent disagreeable taste, more or less nausea or a sense of disgust, dizziness, pain in the forehead and occiput, tinnitus, weight in the epigastrium, etc. With many, the only appreciable symptoms noticed are the unpleasant taste left in the mouth and fauces, and the prompt disappearance of the chills. The dose of the bark, which should be well masticated, is from 2 to 8 grains; but the more desirable form for administration and efficacy appears to be the powdered bark, in capsules, 2 to 5 grains every 3 or 4 hours; as a tonic, grain doses. Of the tincture the dose will vary from 10 to 60 minims every hour or two, and should be given on the days of the attack, commencing several hours before the expected chill. This is certainly an agent that should be thoroughly tested by the profession.
Specific Indications and Uses.—Chronic malarial cachexia and gastro-intestinal disorders depending thereon, with dirty, sallow, or tawny skin, and dirty, pasty tongue; the urine is turbid and cloudy, with urinary deposits. Periodicity, with exacerbations, and remissions, or intermissions.
Related Species and other Antiperiodics.—Alstonia spectabilis, R. Brown. Poelé-bark. Java. Contains, according to Hesse, a much larger proportion of alkaloids than the other Alstonias. Yields echitamine and alstonamine (alstonine of Scharlée).
Wrightia antidysenterica, R. Brown (Holarrhena antidysenterica, Nerium antidysentericum, Linné). Nat. Ord.—Apocynaceae. Conessi bark, Codaga pala, Tellicherri bark. A rusty-hued, spongy, bitter bark, formerly much employed on the continent in dysentery and diarrhoea, and still in use in India. Haines (1858) extracted an impure alkaloid from it, which Stenhouse afterwards obtained pure. The former named it conessine; the latter, wrightine. Its composition has been variously given, and the name kurchicine has also been applied to it. It is amorphous, white, bitter, soluble in alcohol, diluted acids, and ether. As obtained and put on the market by Merck, it forms delicately interlaced crystalline masses. Holarrhena africana contains a similar alkaloid, and is used in Africa as a remedy for dysentery.
Picrorhiza Kurrooa, Royle. India. The root of this plant, known as kali kutki, is used in India as a mild aperient and bitter stomachic. According to Dymock (Mat. Med. Western India), it is a powerful tonic, and is of much value as an antiperiodic, its slightly laxative qualities rendering it doubly efficient.
Echites species.—Several species of Echites are used in India and South America. They and their uses are as follows: Echites syphilitica, Linné filius. Surinam. Used in syphilitic disorders. Echites antidysenterica, Roxburgh, Echites pubescens, Buchanan, Echites longiflora, Desfontaines, Echites Curura, Martins, and Echites insignius, Sprengel; bark used in dysentery and diarrhoea. Echites caryophyllata, Roxburgh; leaves used in arthritic febrile complaints. Echites malabarica, Lamarck; root employed in fevers, and leaves topically to carbuncles.