Hydrastis: Commercial hydrastis - Uses of Hydrastis.

Botanical name: 

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Pharmaceutical Preparations - Medical History - Medical Properties (History) - Bartholow: The Physiological Effects and Therapeutical Uses of Hydrastis

The Detection of Curcuma in Tincture of Hydrastis.—Saturate white filtering paper with the tincture, and allow it to dry. Upon the addition of solution of caustic potassa an immediate orange brown color is produced which gradually assumes a purple hue if curcuma is present, the colors being more or less deep according to the percentage of the latter. Tincture of pure hydrastis is not affected when treated likewise. If a small amount of the suspected tincture be placed in a test tube and caustic potassa added, the orange brown coloration quickly appears if the curcuma is present, even where the paper test fails. Pure tincture of hydrastis, under the same conditions, is not discolored, but rendered turbid, owing to an alkaloidal disturbance. Concentrated hydrochloric acid colors curcuma paper prepared from the tincture a deep reddish brown, which gradually fades to a pink. The hydrastis paper furnishes no coloration. In the test tube, hydrochloric acid furnishes an intense cherry red liquid with the curcuma tincture, but only renders the tincture of hydrastis slightly turbid, and finally a crystalline mass of hydrochlorate of berberine separates, with no coloration. In each of these tests upon mixtures of the tinctures of hydrastis and curcuma, the colorations and their intensity are directly proportioned to the percentages of curcuma.

These reactions are conclusive, and may be summed up as follows.. Neither hydrastis nor tincture of hydrastis affords the color reactions of curcuma or tincture of curcuma. If celastrus root be mixed with the hydrastis, the potash reactions of curcuma may be masked, as the former affords a black or deep brown coloration, according to its percentage, that might predominate the orange brown and purple of curcuma. In this case the hydrochloric acid test serves to detect the latter, since with it the celastrus gives but a very slight reddish coloration, with no pink after-color.

We scarcely consider it necessary to consume more time with this subject. Our work supports the report of Mr. Allaire and Mr. Bassett, and we doubt not that if our pharmacopoeia revisers find it advisable to standardize hydrastis, the act will be followed by an improvement in the quality of the commercial drug.

PHARMACEUTICAL PREPARATIONS.—Fluid Extract of Hydrastis.—The present officinal process for making this fluid extract is as follows:

"Hydrastis, in No. 60 powder, one hundred grammes, alcohol, water, each a sufficient quantity to make one hundred cubic centimeters.

"Mix three parts of alcohol with one part of water, and, having moistened the powder with thirty grammes of the mixture, pack it firmly in a cylindrical percolator; then add enough of the menstruum to saturate the powder and leave a stratum above it. When the liquid begins to drop from the percolator, close the lower orifice, and, having closely covered the percolator, macerate for forty-eight hours. Then allow the percolation to proceed, gradually adding menstruum, until the hydrastis is exhausted. Reserve the first eighty-five cubic centimeters of the percolate. By means of a water-bath, distil off the alcohol from the remainder, and evaporate the residue to a soft extract; dissolve this in the reserved portion, and add enough menstruum to make the fluid extract measure 100 cubic centimeters."—U. S. P., 1880.

This produces a very bitter, dark-colored liquid of a reddish yellow color in thin layer, and upon shaking the bottle that contains it, a deep yellow stain remains where the liquid adheres to the glass. When freshly prepared it is transparent, but it sometimes becomes of a muddy appearance by age. If it be prepared of prime hydrastis, and perfectly percolated, a deposit follows, often within a few days of the time of its preparation. In cool weather, especially if the fluid extract was prepared (as it should have been) in a warm location, this precipitate is abundant, forming a deposit that will perhaps occupy one-fourth the bulk of the liquid. This sediment is largely made up of yellow crystals, and in very cold weather beautiful spangles of crystals form upon the inside of the container. This crystalline sediment is a berberine compound, and in accordance with its production the berberine value of the solution decreases. For this reason, a fluid extract of hydrastis that has precipitated in this manner should be shaken before using it. If it be heated, the sediment mostly dissolves, to re-precipitate when cooled. Taken altogether, we do not feel that the officinal fluid extract of hydrastis is a very acceptable pharmaceutical, but by the crude and simple method of percolation it may be difficult to obtain a more satisfactory liquid by using any menstruum that is a mixture of alcohol and water. Within three weeks' time a specimen that had been made under our direction, very carefully, from prime hydrastis, lost 18.85 per cent. of its berberine by precipitation. [Mr. W. M. Schmitt made, in our laboratory, a number of determinations of the berberine in commercial fluid extracts. This paper will be found in the Pharmaceutical Record during 1885, and is of considerable interest. The variation in percentage of berberine announced by us as taking place inside of three weeks from the time of preparation was in a standard fluid extract made by Mr. Schmitt.] Hence we should not expect the commercial fluid extracts of hydrastis to be of uniform strength even when made of standard hydrastis.

Test.—Transparent fluid extract of hydrastis, when added to a mixture of alcohol three parts and water one part, should form a transparent mixture. It should produce a yellow crystalline precipitate (hydrochlorate of berberine) when mixed with one-fourth its bulk of hydrochloric acid; and a dirty yellowish brown sediment (impure hydrastine) when mixed with an excess of ammonia water. It should yield at least two per cent. of berberine salts by the following assay process:

Mix one fluid ounce of fluid extract of hydrastis with two fluid ounces of a mixture of equal bulks of sulphuric ether and alcohol, and after twenty-four hours decant the overlying liquid. Dissolve the precipitate in two fluid drachms of dilute alcohol, and add one fluid ounce of a mixture of alcohol two parts and sulphuric ether one part, by measure. Allow to stand twenty-four hours, and again decant the overlying liquid and mix with the reserved portion. Then treat the precipitate with one fluid drachm of the above mixture for three successive times, mix with the reserve and filter the mixture. To the filtrate add two fluid drachms of muriatic acid and one-half fluid drachm of sulphuric acid. After an exposure of twenty-four hours in a cool location, separate the crystalline precipitate by means of a filter paper, wash it with a mixture of equal bulks of alcohol and sulphuric ether, until the free acid is removed; then dry it by exposure in a drying closet to a temperature of 125° Fah. and weigh immediately. The yield should not be less than two per cent. of the hydrastis employed; it may reach three and one-half per cent. [If the hydrastis is prime, and the percolation complete, a larger amount of this berberine salt is obtained than by our process (p. 145) for assaying powdered hydrastis. The berberine salt is not as pure, however, and we usually prefer the other method for a direct estimation of hydrastis.] Curcuma is detected by the methods given under powdered hydrastis, using the fluid extract instead of the tincture.

Fluid Extract of Hydrastis without Alcohol.—We object to the foregoing name. If applied to the substances originally introduced, and which the liquids sold under the above name are designed to imitate, it is a misnomer. They certainly were not fluid extracts. The earliest record that we have of such a preparation was about 1874, when the writer prepared for topical purposes a liquid that was to be free from alcohol, and transparent. It gave excellent satisfaction, and came into quite general use, finally being thrown upon the market under various names to distinguish it from the officinal fluid extract. We believe it to be fully as efficacious, and a preferable pharmaceutical, as it is more permanent, and miscible without precipitation with either syrup, glycerine, water, wine or alcohol.

Preparation.—Percolate powdered hydrastis with officinal alcohol until the hydrastis is exhausted. Add to the percolate one-third as much by weight of water as there was of the hydrastis, and evaporate the alcohol. After all the alcohol is driven off, mix with the residue enough cold water to bring the entire weight to two-thirds that of the hydrastis. After twenty-four hours, filter the liquid, and add to the filtrate enough glycerine to bring to the weight of the hydrastis employed.

It will be observed that by this simple process the desirable constituents of the hydrastis are extracted by means of the alcohol, without the gums and inert extractive matters; although the oil and resins are associated in the percolate. The subsequent evaporation of the alcohol and admixture of the residue with water precipitates the oils and resins which are then separated by filtration. Thus a very pure solution of the natural alkaloidal constituents of hydrastis is obtained, and the addition of the glycerine produces a menstruum from which they do not separate by standing, and which will not ferment. This pharmaceutical, in our opinion, and we have made some thousands of pounds of it, is preferable to the officinal fluid extract. It can be administered whenever that substance is indicated and as an injection, or wash, is admissible in many cases when the fluid extract can not be employed. We hope that a similar preparation may become officinal. It will be observed that the process is such as to forbid the name fluid extract, unless the product is made officinal under that term, and we believe that the proper location is among the liquors. We therefore prefer the name Liquid Hydrastis, having used it for many years. We reproduce our description of this pharmaceutical as follows:

"Liquid hydrastis has a beautiful, deep yellow color, and when shaken, stains the bottle clear yellow. The taste is bitter, but not unpleasant and nauseating, like some bitter drugs. There is no odor of alcohol, none being present, but it possesses the exact odor of fresh powdered hydrastis. It will mix with water, glycerine, wine, or syrups, in any and all proportions, and the mixtures will not become turbid. It will not ferment, and the freezing point is much less than that of water. It contains all of the alkaloids and acids of hydrastis, in their natural combinations."

Tincture of Hydrastis.—This is officinal, as follows., "Hydrastis, in No. 60 powder, twenty parts. Diluted alcohol, a sufficient quantity. To make one hundred parts.

"Moisten the powder with fifteen parts of diluted alcohol, and macerate for twenty-four hours; then pack it in a cylindrical percolator, and gradually pour diluted alcohol upon it, until one hundred parts of tincture are obtained."—U. S. P., 1880.

The chief feature in connection with this pharmaceutical is the difference in menstruum used in it and that of fluid extract of hydrastis. If this tincture were designed for a different purpose than the fluid extract, this change would perhaps be obvious; or, if the menstruum of either were incapable of extracting the increased, or decreased amount of hydrastis of the other. In our opinion, tincture of hydrastis should be made of the menstruum, employed in producing the fluid extract, for the increased amount of alcohol will not affect its administration. [When admissible, we favor a uniformity in the menstruum that is used in making both the tincture and fluid extract of a given drug. Conditions may possibly exist in which a break is necessary, but we think that as a rule it will be found that a menstruum best adapted to making one of these preparations in the one to use with the other.]

Essence of Hydrastis. [This essence, or mother tincture as it is called, of hydrastis is the only pharmaceutical preparation of hydrastis used in homoeopathic medicine, and peculiar to homoeopathists. From it, in the usual manner, their dilutions are made. Homoeopathic physicians use the alkaloidal salts defined by us in preceding pages.]—The Pharmacopoea Homoeopathica Polyglotta recognizes this preparation as follows: The rhizome (fresh root) is pounded to a fine pulp and weighed. "Then two parts by weight of strong alcohol are taken, and after thoroughly mixing the pulp with one-sixth part of it, the rest of the alcohol is added. After having stirred the whole well, and having filled it into a well-stoppered bottle, let it stand for eight days in a dark, cool place. The essence is then separated by decanting, straining and filtering."

MEDICAL HISTORY.—The root of this plant was highly prized as a dye by the North American Indians on account of its yellow coloring matter, and also for its medicinal value; but Kalm, in 1772, Cutler, in his Indigenous Vegetables, 1783, and Schoepf, in his Materia Medica Americana, 1785, overlooked it. This seems remarkable when we consider the important position that hydrastis occupied with the various tribes of Indians and with our settlers. Although the Indians introduced hydrastis to the whites (see medical properties), and it has always been a domestic remedy, it was reserved for Barton to bring the plant before the medical profession. The first medical reference that we have been able to find occurs in Barton's Collections for a Vegetable Materia Medica, 1798 (part first), wherein credit for its introduction is given the Cherokee Indians. In the third part of this work, page 13 (1804), he devotes considerable attention to the drug, and mentions the fact that it -supplies us with one of the most brilliant yellow colors with which we are acquainted." From this date until the appearance of Rafinesque's Medical Flora of the United States, 1828, nothing of importance was published in medical literature, and nothing added to Barton's remarks. His statements were either copied verbatim or condensed by writers upon materia medica, although few gave him any credit for his work. [Captain Lewis (of the Lewis and Clarke expedition) attached a paper to his herbarium specimens of Hydrastis canadensis, May 24th, 1804, in which attention is called to the fact that" it is said to be a sovereign remedy" in eye diseases, and prized by the inhabitants of the country where it grows. This paper was not published until 1834, when it appeared in the American Journal of Pharmacy, p. 201.] Rafinesque next (1828) devoted considerable space to this plant, and produced a rude figure of it. [This figure has been reproduced, time and again, by subsequent authors, and in no instance have we found a credit given to Rafinesque's work. His engravings seem to have been considered as common property, and few, it any copyists, had the courtesy to acknowledge the source.]

In 1833 a paper from the editor of the Thomsonian Recorder appeared in that work (Vol. I., p. 397) which was the most important communication we have been enabled to find to that date. This paper gave a synopsis of the previously ascribed values of hydrastis, and added the uses Dr. Thomson made of it and the position it occupied in Thomsonian practice. [Hydrastis seems not to have been a conspicuous remedy of the early Thomsonians. It was mentioned in a paper which appeared in the Thomsonian Recorder, 1834, p. 313, entitled, "The Materia Medica of Dr. Samuel Thomson's Guide and Narrative, being a correct catalogue of all the plants recommended by him," but it occupied little space in his works. Many of Thomson's early followers scarcely recognized it. Comfort's "Practice of Medicine on Thomsonian Principles" gives but a brief notice of hydrastis.]

Beach introduced hydrastis into the first edition of his American Practice of Medicine (1833), and it has always been an important member of the materia medica of his followers. [Hydrastis was in reality brought out by the Eclectics, and is often known as an Eclectic Remedy. Prof. John King has valued it since 1833. The late Wm. S. Merrell introduced its products perhaps more extensively than any other person. In connection with this subject, it should be recognized that Dr. Walter Beach and the early Eclectics worked together.]

The United States Dispensatory, first edition, 1833, omitted hydrastis, but the second edition, 1834, gave it a brief consideration in the appendix. [This unimportant notice passed unchanged through nine editions of that recognized authority, and was only slightly enlarged in the tenth edition, 1854, occupying still a position in the appendix. In the twelfth edition, however, it was placed in the primary department, the plant having been honored by an officinal position in the Pharmacopoeia of 1860.]

Between this date and 1852 the standard works upon materia medica usually noticed the plant, but very briefly, and really added nothing to the preceding literature. Short extracts were usually made from the works of Barton, Rafinesque, Beach, or Thomson, the selection of authorities being usually in accordance with the affiliations of each writer. Hydrastis had, however, at this time become a recognized remedy. In 1852 King's Eclectic Dispensatory appeared, and hydrastis was highly recommended as an Eclectic remedy, in the following language: "This remedy is peculiar to Eclectics, and ranks among their best articles." In that work the medical uses and properties of hydrastis were prominently drawn by Prof. King, thus bringing the plant conspicuously before the Eclectic section of the medical profession. About this date interest was excited in certain products of the plant which were at that time commencing to be liberally advertised. These facts, together with frequent contributions from physicians who wrote for the Eclectic Medical Journal of Cincinnati, produced an extensive demand for the plant and its products, although this demand was almost exclusively among Eclectics. Hydrastis rapidly became more popular, however, and soon overstepped the bounds of sectionalism. In 186o it was made officinal in the United States Pharmacopoeia.

In the Regular section of medicine, Prof. Roberts Bartholow has given considerable attention to hydrastis, as is indicated by his paper on the subject in the various editions of his Materia Medica, and our readers are indebted to this author for a communication that follows regarding the uses of hydrastis. In 1862 hydrastis excited interest sufficient to merit a paper from Prof. Bentley, of England, under the heading, "New American Drugs," which appeared in the Pharmaceutical Journal and Transactions, 1862, p. 540, but which was mainly devoted to a consideration of the proximate principles of the plant. This is the only important foreign contribution we have in the early medical literature pertaining to this plant, although in 1873 Dr. Van der Espt presented a lengthy paper to the Royal Society of Medicine and National Sciences, Brussels, Belgium, without, however, adding any new facts; and recently the plant has excited some little attention in Germany. [The recent literature upon the therapeutics of hydrastis will be considered in the medical contributions of our contributors.] It has steadily grown in favor, all schools of medicine use it, and many members of each school value it very highly. The converse is also true, and many physicians neglect it, while others do not use it at all.

MEDICAL PROPERTIES (HISTORY).—In 1798 Prof. B. S. Barton issued the first part of his "Collections for an essay towards a Materia Medica of the United States." In it he writes, p. 9. "I am informed that the Cherake [Cherokee Indians.—ED.] cure it [cancer] with a plant which is thought to be Hydrastis canadensis." In the third part of his "Collections," 1804, he again refers to hydrastis: "The root of this plant is a very powerful bitter" (p. 13), and says (p. 14): "The hydrastis is a popular remedy in some parts of the United States. A spirituous infusion of the root is employed as a tonic bitter in the western parts of Pennsylvania, etc., and there can be no doubt that both in this and in other shapes, our medicine may be used with much advantage. An infusion of the root in cold water is also employed as a wash in inflammations of the eyes." [Rafinesque's Medical Flora, Vol. I., 1828, p. 253, adds: "It is considered a specific by the Indians for that disorder." Captain Lewis, 1804 supports the above, saying: "It is said to be a sovereign remedy in a disorder common to the inhabitants of the country where found, usually termed sore eyes."]

Hand (House Surgeon, 1820,) adds:" It may be given in form of powder or of strong tea made by boiling, in indigestion, the secondary stages of low fevers, and all cases of weakness in general."

Rafinesque's Medical Flora, 1828, Vol. I., pp. 253 and 254, supports the foregoing, and in addition states that" they [natives] also employ it for sore legs and many external complaints as a topical tonic. Internally, in infusion or tincture, in disorders of the stomach, the liver, etc. It appears to be slightly narcotic and available in many other disorders. Some Indians employ it as a diuretic, stimulant and escharotic, using the powder for blistering [This must be a mistake; phytolacca, or sanguinaria, will blister, but hydrastis can not be used for this purpose.] and the infusion for dropsy." In Elisha Smith's Botanic Physician, 1830, we find several compounds containing hydrastis, to-wit: "Stimulating Cathartic Powders," "Bone's Bitters," and "Tonic Powders." Howard's Improved System of Botanic Medicine, 1832, p. 327, recommends it, also, in dyspepsia. Beach (1833), American Practice of Medicine, states that in connection with tonic properties it is "at the same time laxative, which makes it very appropriate in dyspeptic disorders." Next, the edition of the Thomsonian Recorder of 1833, p. 398, reviewed the medical properties as previously announced by others, and added to them as follows: "The importance of this article, taken in teaspoonful doses, for the relief and removal of bowel complaints in children should be extensively known. It is not only a corrector of the stomach, a regulator of the bowels, and a vermifuge for children, but it is an admirable remedy for the peculiar sickness attendant on females during their periods of utero-gestation, called morning sickness. It admirably relieves stomachic oppression, nausea, and heart-burn." Of the use of hydrastis in sore eyes he writes: "It is not a decoction of the dried root in boiling water that relieves ophthalmia, but is the freshly dug root, well cleansed and bruised, and infused in cold. soft water, that is to be particularly relied upon." [In contradiction to the fresh root part of this statement we quote from Captain Lewis, 1804. In speaking of the eye troubles of the settlers, he remarks as follows: "This disease is a violent inflammation of the eyes, frequently attended with a high fever, and sometimes terminates in the loss of sight, always gives great pain, and continues for a length of time in most cases. The preparation and application of this remedy is as follows: Having procured a sufficient quantity of the roots, wash them clean and suffer them to dry in the shade, break them with the fingers as fine as you can conveniently, put them in a glass vessel, taking care to fill it about two-thirds with the broken root, add rain or river water until the vessel is filled, shake it frequently and it will be ready for use in the course of six hours. The water must not be decanted, but remaining with the root is to be frequently applied by wetting a piece of fine linen and touching the eyes gently with it."—Am. Journ. Pharm., 1834, p. 201.] Sanborn's Medical Botany, 1835, p. 63, states that the Indians use hydrastis as a diuretic. If the root be chewed it will cure white aphtha or ulcers in the mouth. [We have testimony to the fact that in portions of Kentucky hydrastis is the domestic remedy for ordinary forms of sore mouth. The patient simply chews small fragments of the root from time to time. After chewing the root, if the saliva be applied to indolent sores, beneficial results are said to follow.—L.] Kost (Elements of Materia Medica and Therapeutics) states that it is good as an application in infusion to inflammations of the mucous tissues, leucorrhoea, blenhorrhoea, etc., and is of value in erysipelas. Dunglison (Medical Dictionary, 1852, p. 450) is the authority for a statement to the effect that in Kentucky hydrastis is used as an outward application in wounds. [We have an extensive acquaintance in several sections of Kentucky, and have known of infusions of hydrastis being applied to indolent ulcers as a stimulant, but have never known it used on fresh wounds.]

In 1852 Prof. John King issued the first edition of his dispensatory, under the title, "The Eclectic Dispensatory of the United States of America," and therein gave the medicinal uses of hydrastis a more careful review than had previously been awarded, although many of the values that early writers had ascribed to the plant were omitted as being overdrawn. [It is too true that many of these assertions regarding the uses of a drug are unsupported by a single fact that will bear the light. Empiricism in medicine seems to have been a necessity, for our most valued remedies have been handed down to us by men who scarcely recorded a systematic line of investigation. Indeed, we must go back to the aborigines time and again. It is to be hoped that the day will come when medical men as scientists will unite to demonstrate facts, to glean the grain from the chaff. Then as this or that statement is verified or disproved, we trust that a spirit of charity will prevail for those who were misguided, for these same men will be found to have announced many valuable truths.] The indications for the administration and use of the drug and its preparations were carefully discussed in that work, and the remedy was thereby brought legitimately before the Eclectic branch of the medical profession (see Medical History), and in consequence of its general adoption by Eclectics it was from that time generally known as an Eclectic medicine. King was first, that we can find recorded, to recommend the plant in gleet and chronic gonorrhoea, and he wrote: "I have used this preparation likewise with much success in incipient stricture, spermatorrhea, and inflammation and ulceration of the internal coat of the bladder." From that time hydrastis was a popular remedy. It became officinal in 1860, and it now occupies a higher position than at any previous day, and the Homoeopathic branch of the medical profession also use it extensively, as is shown by Prof. Hale's paper on the subject.

We have endeavored in the foregoing pages to give a plain, systematically connected record of the introduction of hydrastis into medicine, and its past uses. Modern investigations have disproved many of the statements of other times, but writers still differ considerably from each other, and there is yet room for investigation. This plant is of such importance as to merit more attention than our brief medical record, and we are pleased to present the following independent papers from leading representatives of the various bodies of practitioners.

THE PHYSIOLOGICAL EFFECTS AND THERAPEUTICAL USES OF HYDRASTIS. (Written for this publication by Prof. Roberts Bartholow, M. D., LL. D., of the Jefferson Medical College of Philadelphia.) [Dr. Bartholow desires to acknowledge his indebtedness to Dr. A. B. Brubaker, Demonstrator of Physiology in the Jefferson Medical College, for valuable assistance in conducting the experiments.]—But little attention has, heretofore, been given to the physiological actions of hydrastis. It is true Schatz, [Centralblatt für gesammte Therapie, Band 2, p. 82.] Felluer, Sclavatinsky, and some others, [Meditz. Horz, No. 16, 1884. Quoted from the London Med. Record for November 15, 1884.] have made some studies, but their results differ so widely from those herein detailed that it may be questioned whether they operated with sufficiently good specimens of the drug. The alkaloid hydrastine with which the following experiments were made was sent to me by Prof. J. U. Lloyd, the editor of this Journal, who is, I hope I may be permitted to say, unimpeachable authority. As hydrastine is quite insoluble, a solution of the hydrochlorate was prepared for me by Messrs. John Wyeth & Bro., which contained 33 per cent. of the salt. The effects of the alkaloid were compared with those of the fluid extract. As the actions of hydrastis consist of the sum of the effects of its active constituents, it is necessary to know how far each contributes to the results. It was soon ascertained that the alkaloid hydrastine is the true active principle-for the very characteristic effects of this were simply repeated by sufficient doses of the fluid extract. The latter is, as might be expected, slower in action, but in respect to the manner of action there was between them no appreciable difference. Three grains of the hydrochlorate caused the death of a frog in four minutes, whilst forty minims of the fluid extract proved fatal in twelve minutes, the mode and character of the action being the same. The results in rabbits were corresponding. In general terms, the effects of hydrastis are those of hydrastine in both classes of animals, but minute differences may hereafter be detected on closer examination.

General Effects of Hydrastine Hydrochlorate in Cold-Blooded Animals.—When ten minims of the 33 per cent. solution are injected into the abdominal cavity of a frog, the following phenomena ensue: In two minutes, muscular rigidity is manifest, with extension of the limbs and inability to move; in three minutes the cutaneous reflex is so heightened that the gentlest tap on the skin causes a tonic convulsion from above downwards; successive tonic convulsions then ensue, with fibrillary trembling between, until at the end of four minutes death occurs in a strong tetanus. On opening the chest, the heart is still found in action, but in a few minutes more ceases in diastole, all the cavities being full of blood, and its muscular tissue is found to be irresponsive to electrical irritation.

In a rabbit weighing about fifty ounces, forty minims of the same solution, or thirteen grains, caused death in five minutes with the same phenomena—that is, with successive tetanic convulsions, the head drawn forcibly back, the limbs extended, and the respiration fixed, with increasing cyanosis of the ears and mouth. The heart continues in action after respiration has entirely ceased, and on opening the chest then it is still found in slow movement, the auricles most active and all the cavities distended with blood. The muscular tissue of the heart, does not respond to electrical or mechanical irritation.

It follows from the foregoing that hydrastis belongs to the group of excito-motor agents. It heightens preception, the cutaneous excitability and the reflex functions, and it causes death by tetanic fixation of the respiratory muscles.

Determination of the seat of the actions, whether spinal or peripheral.—A frog weighing about twelve ounces was pithed. After division of the medulla, the whole length of the spinal cord was carefully destroyed. No other injury was done, and very little blood lost. Ten minims of the hydrastine solution were then thrown into the peritoneal cavity. The frog remained perfectly limp and flaccid, and no spasm or convulsion of any kind occurred. The heart, on opening the chest some time after the death of the frog, was no longer in movement, the action having ceased in the diastole, and the cavities, as in other instances, were distended with blood.

The spasms and convulsions caused by hydrastine are, therefore, central or spinal, and not peripheral.

Has hydrastine any effect on the peripheral nerves and muscles?—To ascertain this, the left sciatic nerve was dissected out, isolated and a strong ligature applied around the limb the nerve excluded, thus cutting off the circulation from the parts below. Ten minims of the hydrastine solution were now thrown into the abdominal cavity. The usual effects followed—stiffness, rigidity and spasm of the muscles, general tonic convulsions, and intermediate fibrillary contractions. On stimulating the sciatic of the ligatured limb, contractions, not active, of the gastrocnemius followed; but on direct excitation of the unpoisoned muscles of the calf, they responded readily. In the other, the poisoned limb, feeble contractions of the calf muscles ensued on stimulation of the nerve, and similar contractions took place when these muscles themselves were directly acted on. After a time when the influence of the hydrastine had attained the maximum, and immediately after suspension of respiration, both nerves failed on stimulation to excite muscular contractions, and the poisoned muscles became entirely inexcitable.

The foregoing experiments prove that hydrastine exhausts the irritability of motor nerves and muscles.

Action of Hydrastine Hydrochlorate on the Heart.—A freshly removed frog's heart suspended in the solution, rapidly loses its electric excitability, and in a minute no longer responds to a strong current. Applied to the exposed heart in situ, the same effect is produced more slowly, and in five minutes an arrest of the movements takes place in diastole, the cavities being fully distended with blood. The auricles resist the action somewhat longer.

The pneumogastrics being divided, ten minims of the solution are injected into the abdominal cavity. The heart is acted on more slowly, and its excitability to stimulation, electrical and mechanical, although much feebler than the normal, still persists. On excitation of the peripheral end, the heart is rather lazily arrested. In the previous experiments, the heart undisturbed in its anatomical relations, it was found that the excitability of the vagus, just before the cessation of respiration, was entirely destroyed, and at the stoppage of the heart's movements, its muscular irritability was lost.

From these experiments we learn that hydrastine acts both on the inhibitory and motor apparatus, destroying their power of response to excitation, but the former function yields later, or after the latter.

To determine more precisely the nature of the action exerted on the cardiac motor and inhibiting apparatus, the vagus was first paralyzed by atropine, and then the usual dose of hydrastine administered. The increased movement caused by atropine was soon lessened by hydrastine, and the heart, after the cessation of the respiratory movements, was ultimately arrested in the diastole, the cavities fully distended as before described. The effect of the atropine was now exhibited in the preservation of the irritability of the heart muscle. In the experiments before detailed, it was found that hydrastine destroyed the irritability of the heart muscle, but when atropine was administered, the response to mechanical and electrical irritation was retained.

Foldout. The Action of Hydrastine on the Blood Pressure.—A chloralized rabbit weighing about fifty ounces was used for the purpose. The right carotid artery was connected with the manometer and the revolving cylinder in the usual way. The attached tracing exhibits the effects of hydrastine. Up to the point a the pressure was at the normal for a rabbit under the influence of chloral, and then began the effects of the drug. It causes, as the tracing shows, some lowering of the blood pressure. The sudden rise at b was due to a convulsion, the quantity of chloral not being sufficient to prevent them entirely.

Antagonism between Hydrastine and Chloral.—The number of experiments has been too small to formulate positive conclusions, but enough has been learned to indicate that chloral antagonizes to a large extent the increased reflex excitability and the tonic convulsions caused by hydrastine. It is probable, indeed, that the antagonism will be found as extensive in range as between chloral and strychnine. Thus far I have not had the opportunity to ascertain the lethal dose of hydrastine. Until that is determined, the power of its physiological antagonists can not be measured with accuracy. Further experiments are making on this point, and will be announced hereafter.

Strychnine and Hydrastine.—A remarkable correspondence can be traced between the actions of strychnine and hydrastine, but the power of the former seems to be the greater, whilst in extent of action the latter seems far more. Both exalt the reflex function of the cord; both induce tetanic convulsions, and both cause death by arrest of the respiratory movements in a tonic spasm. Hydrastine more affects the peripheral nerves and muscles, and to a much greater extent impairs the contractility of the cardiac muscle.

The Therapeutical Applications of Hydrastis.—As the results obtained from the administration of hydrastis constitute the sum of the actions of its several constituents, it may be best to consider the powers of the active principles separately, before treating of the effects of the drug as a whole.

The plants containing berberine are, as a rule, members of the tonic and reconstituant group. Hydrastine being peculiar to hydrastis, much of the effect produced by this agent must be due to the presence of this principle. Prescribed alone, hydrastine has been supposed to have the effects of a tonic, antiperiodic, and to some extent alterant—a term used to signify the power to promote the waste and excretion of morbific materials. The physiological study of hydrastine, as made by Schatz, Fellner, Slavatinsky, and others, [Centralblatt für die gesammte Therapie, Band 2, p. h, and Meditz. Obozr. No. 16, 1884. The latter, quoted by London Med. Record, Nov. 15, 1884.] has not contributed to the subject of its therapeutical power, although it forms a groundwork for the therapy of the future. If, however, the physiological actions as detailed in this paper be confirmed by subsequent researches, quite a new phase will be given to its therapeutical applications.

As the fluid extract contains all the constituents of hydrastis, it is the most concentrated form available for administration and, therefore, will be the best preparation for procuring the effects of the remedy as a whole, whether given by the stomach or applied externally.

Hydrastis in Gastro-Intestinal Disorders.—As a stomachic tonic, when the condition of the stomach is that of debility, as we find it in atonic dyspepsia, so-called, and in convalescence from acute diseases, hydrastis serves a useful purpose. In common with the bitters, it stimulates appetite and increases the secretion of the gastric glands. Disposing thus of an increased supply of aliment, the constructive metamorphosis is promoted. For this purpose, it is best to administer ten to twenty drops of the fluid extract a few minutes before meals.

Both the alkaloids of hydrastis, exerting an inhibitory influence on fermentation, the fluid extract can be given with excellent effects in cases of catarrh of the stomach accompanied with fermentative changes in certain foods, whether or no, the Sarcina Ventriculi be present. The result of the action will be more permanent than the above remark implies, seeing that this remedy can modify, if not remove, that alteration of the mucous membrane which is accompanied by an outpouring of pathological mucus. To effect this purpose it were better to administer the fluid extract, two or three hours after meals, and the dose should range from fifteen to thirty minims.

As a tonic and reconstituent in the classes of cases above mentioned, quinine is now largely used: it is quite certain that hydrastis can be substituted for the most part with advantage.

The experiments of Rutherford [The British Medical Journal, 1879, Vols. I. and II. Report of the Committee of the British Med. Association, etc.] have confirmed the belief, founded on empirical observations, that hydrastis is an hepatic stimulant, although not one of the most active. As he operated with "hydrastin" so-called, which consists for the most part of berberine, it is probable that the results which he obtained are not equalled by those produced by the exhibition of the fluid extract. Hydrastis has been found useful in gastro-duodenal catarrh, associated with catarrh of the bile ducts-a morbid condition in which the output of bile is lessened by the mechanical obstruction, and the intestinal digestion is impaired in consequence of the insufficient supply of bile, the fermentative changes set up by the mucus which plays the part of a ferment, and the consequent absorption of imperfectly prepared materials. In this state of things we find the true explanation of some cases of jaundice, of most cases of "biliousness," and the initial changes of lithaemia.

The gastro-duodenal catarrh of chronic alcoholism is a condition in which the use of hydrastis has a decidedly beneficial effect, and the improvement in the digestion has seemed to lessen the appetite for alcoholic stimulants. This statement, made by several observers, [The Practitioner, London, Vol. XVI., p. 121, et seq.] has been rather sarcastically commented on by the authors of the National Dispensatory, [Third edition, p. 798.] who are, however, pessimistic if not nihilistic in their therapeutical conceptions. The new facts, demonstrating the effects of hydrastine as a spinal stimulant, are additional reasons for supposing it to be possessed of the powers claimed.

For the relief of the intestinal troubles above mentioned, the fluid extract of hydrastis should be given in the interval between the meals, and the dose should be larger (ʒss-ʒi) than in the case of the corresponding stomachal troubles.

As an antipyretic and antiperiodic, the alkaloid—hydrastine—has had no adequate clinical study. Twelve years ago, I made some experimental trials at the Hospital of the Good Samaritan, in Cincinnati, in seven cases of tertian intermittent. White hydrastine in crystals was furnished me by Prof. E. S, Wayne, M. D., of Cincinnati, the well-known chemist and pharmacologist. Two of the cases were recent, uncomplicated, and but a few paroxysms had occurred. Twenty grains of hydrastine, administered in three doses, in anticipation of the seizure, merely modified its violence, but did not prevent it in either case. The second attempt proved successful. Three of the cases more chronic in character required sixty, sixty-five and eighty grains respectively. The two remaining proved still more rebellious, and the patients becoming uneasy, I was forced to resort to quinine. The supply of pure hydrastine was not sufficient to carry on further experiments, and a suitable opportunity to resume the investigation not occurring, I have no further clinical experience in this direction to report. [The remarkable activity of the pure hydrastine furnished me by Prof. Lloyd, necessitates caution in its administration, until its lethal power in man can be determined. It is now evident that the hydrastine used by me formerly in the treatment of diseases was not pure. I must therefore caution my readers in respect to the administration of the pure alkaloid, and especially its salts, and warn them not to employ this active agent, as they have heretofore been giving berberine, or a mixture of hydrastine and berberine.] Nevertheless, these trials, whilst not numerous, are at least significant. They indicate the possession of real antiperiodic power, inferior to quinine, it is true, but apparently inferior only to the great antiperiodic. Since that time, the chemist's skill has produced by synthesis various products approaching in composition closely to quinine, and possessed of powers very similar but still inferior. It may be that under these circumstances, hydrastine will never rival quinine or its analogues, but the powers which it is now shown to possess may require a different statement hereafter.

Topical Applications.—For local use, the best mode of applying hydrastis is in the form of the fluid extract, which may be employed undiluted or diluted with glycerine. Its staining power is an objection, since the color which it imparts to cotton cloth, if not permanent, is at least not readily washed out.

The fluid extract of hydrastis is an excellent topical application in cases of catarrhal inflammation of the mucous membranes. In nasal, faucial, uretheal and vaginal catarrh, and in otorrhoea and conjunctivitis, there can be no doubt of its good effects. It may be applied freely in the undiluted state without fear of injury, if no good be accomplished by it. It has proved to be a very efficient injection in gonorrhoea, more especially after the acuter symptoms have subsided. For this purpose it may be diluted with glycerine or mucilage, or both, to the required extent. Formerly when I used to see these cases in considerable numbers, I found it a capital application in cervicitis. I had, also, excellent results in such cases, and in gonorrhoea, from "hydrastine" suspended in mucilage.

To express a final judgment as to its therapeutical value, my conviction is that hydrastis is a useful remedy, and well deserves a trial in the various conditions in which it is recommended above.

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Drugs and Medicines of North America, 1884-1887, was written by John Uri Lloyd and Curtis G. Lloyd.