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Ergota (U. S. P.)—Ergot.

[image:12579 align=left hspace=1][image:23161 align=left hspace=1]Preparations: Tincture of Ergot - Infusion of Ergot - Extract of Ergot - Fluid Extract of Ergot - Liquor of Ergotin - Wine of Ergot
Related entry: Ustilago.—Corn-Smut

SYNONYM: Ergot of rye.
"The sclerotium of Claviceps purpurea (Fries), Tulasne (Class: Fungi), replacing the grain of rye, Secale cereale, Linné (Nat. Ord.—Gramineae). Ergot should be only moderately dried. It should be preserved in a close vessel, and a few drops of chloroform should be dropped upon it from time to time to prevent the development of insects. When more than one year old, it is unfit for use"—(U. S. P.).
Nat. Ord.—Fungi—Ascomycetes.
SYNONYMS: Spur, Spurred rye, Smut rye, Ergot of rye.

History and Formation.—Ergot is the sclerotium, the second, intermediate, or dormant stage of Claviceps purpurea (Fries), Tulasne, a fungus replacing the grain of rye (Secale cereale, Linné). Ergot, or spur, as it is sometimes called, was formerly regarded as a diseased grain of rye, but as now understood the grain of rye is simply replaced with the fungous growth. No transformation occurs as was supposed, but the tissue of the caryopsis of the rye is destroyed (Pharmacographia).

Ergot has been the subject of much investigation, particularly at the hands of Léveillé, Meyen, Tulasne, and others. De Candolle (1816), believing with others that ergot was a distinct and complete fungus, named it Sclerotium Clavis, while Fries denominated it Spermoedia Clavus. Queckett called it Ergotoetia abortifaciens, and Berkley, Oidium abortifaciens. Tulasne, however, placed it in the genus Claviceps, as an ascomycetous fungus, of which he described 3 species—one of which, the Claviceps purpurea, grows on rye, wheat, oats, and numerous pasture grasses. For a long period the ergotized condition of the rye was confounded with other and somewhat similar conditions met with in other cereals and in the fruits of sedges and grasses—parasitic maladies of crowded herbaceous plants growing side by side, year in and year out, in the same localities. The affection of the rye has been more thoroughly studied than some of those in other plants, probably on account of the former general use of rye as a food and the terrible consequences of epidemics of gangrene that have been traced to the contaminated grain, and also from the fact that it is one of the most important of medicinal substances.

The generic name of the fungus, now recognized as the causative factor in the production of ergotized rye is Claviceps, and is derived from the club-headed receptacles bearing the fructifications; the specific name, purpurea, refers to its purplish hue. The intermediate stage of the fungus is designated the sclerotium, spur, or ergot. Sclerotium signifies a hardened body, and ergot, derived from a French word (argot, a cock's spur), has reference to the spur-like shape of the sclerotium. The effect of the Claviceps, or fungus, is to apparently change the young fruit into an elongated, purplish-black, hard body which projects from the fruiting head of rye. This body is subcylindrical, curved, tapers bluntly at each extremity, and is an inch or more in length. Its outer surface is dark, being purple-black, while its interior is white and felt-like, being, in fact, "a densely compacted mass of fungus mycelium" (spawn, or branching network of hyphae, which latter are thread-like bodies or cells, having a protective membrane of cellulose inclosing protoplasm). Besides the protoplasm the mycelium cells contain about 35 per cent of oily food materials. The dark, spur-like body is the ergot, and Léveillé, a French botanist, was the first to show it to be an aggregation of mycelium at rest and not, as formerly supposed, a diseased grain.

Tulasne (18.52), desirous of learning the fate of these bodies (ergot) after leaving the host plant (the rye), instituted experiments which led to the determination of the true character of ergot and the fungus of which it is a part. He began his experimentation by sowing a number of the sclerotia (ergot), and these, after remaining at rest upon damp earth for several months, began to put forth from their surfaces little nodules or hillocks which, by lengthening, formed rodlike projections (stipes) of thick, white material, capped at the free extremity with plump, rounded expansions or heads (stroma) of a violet color. At first these club-like projections were thought to be distinct parasites, but were later proven to be mere expansions of hyphae growing out from the mycelium cells constituting the sclerotium, and pushing their way from their point of origin in the pale-white interior through the thin-purple coat. In time the surface of the little purple head or stroma was found to have developed minute papillae, or wart-like projections, each presenting a minute orifice at its apex. The opening led directly into an ovoid cavity, directly below the papillae, known as the perithecium (conceptaculum). Subsequently there arose from the base of this ovoid cavity (perithecium) long, thin, tubular bodies, denominated asci or thecae (sporesacs), as well as other asci in various stages of development. Inasmuch as the orifice of the papillae leads vertically downward into the perithecium, the asci, whose long axes are also vertical to the surface of the stroma, point toward the orifice in the papillary elevation. Within each of these asci there are long, slender, thread-like bodies without color, and from 6 to 8 in number, termed ascospores. As these silky-white flocculent spores ripen they are shed as an agglutinated mass through the small orifices of the papillae by the bursting of the asci, and are then carried about by insects, rains, winds, and like agencies. This usually takes place at about the same time that the cereals are beginning to blossom. If now the ascospores, come in contact with the young flower of the rye, the latter is infected in the following manner, the result being that the mycelium takes possession of the base of the pistil. At various points the ascospores swell, and at these swellings give rise to small, slender branchlets, which quickly bore through the epidermis at the base of the flower. In about 10 or 12 days the lower portion of the flower is found to have been invaded by the mycelium, the slender, colorless hyphae of which soon project from the surface and envelop the young pistil in complex folds. From the tips of the hyphae, which terminate these folds, there "buds off" enormous numbers of very minute, colorless bodies, termed conidia, and at the same time the folds secrete a malodorous but viscid and sugary fluid of a yellowish color, which repels bees, but attracts flies, beetles, ants, etc., and is popularly known as the "honey dew." This saccharine fluid, in which are immersed the conidia, sticks to the proboscides, feet, and other parts of the visiting insects, and is thus carried to healthy flowers, where the conidia, in contact with the young flowers, behave exactly as do the ascospores—germinating and penetrating the pistil-base and developing in it a mycelium exactly like that produced by the latter, and which, in a few days, produces new conidia and fresh honey dew, thereby establishing a new source of infection.

The white mycelium and the honey dew with its contained conidia, constitutes what was formerly known as the sphacelia, a term indicative of the shrivelled gangrenous appearance of the tissues attacked. After the production of conidia and honey dew has progressed for several days, the pistil which normally would have developed into the grain, becomes a dead, shrivelled mass. The fact has already been referred to that the mycelium, which gives origin to the conidia and honey dew, has penetrated the floral base and pistil, forming in their tissues a dense, white felt-work. This now becomes more and more compact and increases in quantity, while the outer cells become first dark in color and then hard in texture, thereby developing the sclerotium of the fungus—the ergot, which, as its growth progresses and it becomes an elongated, spur-like body, carries before it the shrivelled, dead remains of the pistil and the sphacelia, which gave origin to the conidia. Thus the ergot matures just previous to the time for harvesting the rye and then drops off, rests upon the ground through the winter and early spring months, and in the summer germinates, and thus the ravages of the previous season are repeated. In this way it may go on for years, producing its sphacelia and developing its ergot parasitically upon the host plant, and then, after resting on the soil through the winter, it saprophytically develops its stromata upon the ergot-form or sclerotium.

It will be observed from what has been narrated, that the life history of Claviceps presents 3 stages of development: (1) The development of the sphacelia, with its conidia and honey dew; (2) the dormant state of the compact mycelium of the fungus, or the produced ergot; (3) the fructification of the ergot exhibited in the germination of the ergot-form producing the stromata, perithecia, asci, and ascospores. The ergot, therefore, is but the intermediate or resting stage of the development of this interesting fungus (Claviceps purpurea). The major portion of the preceding popular description of the formation of ergot was prepared from H. Marshall Ward's Diseases of Plants.

Ergot should be gathered previous to harvest, and is said by M. Bonjean to be much more active after the fifth day of its formation. When we examine a number of ears of ergotized rye, we find that the number of grains on each spike which have become ergotized varies considerably; there may be one only, or the spike may be covered with them. Usually the number is from 3 to 10. The mature ergot projects considerably beyond the paleae. It has a violet-black color, and presents scarcely any filaments and sporidia. Ergot is met with in all climes where cereals are grown, the bulk of the commercial product coming from Vigo, in Spain and Teneriffe, while considerable quantities are furnished by southern and central Russia (see Pharmacographia).

Description.—Ergot of commerce consists of grains which vary in length from a few lines to 1 inch, or even 1 1/2 inches, and whose breadth is from 1/2 to 4 lines. Their form is cylindrical or obscurely triangular, with obtuse angles, tapering at the extremities (fusiform), curved like the spur of a cock, unequally furrowed on two sides, often irregularly cracked and fissured. The odor of a single grain is not detectable, but of a large quantity is fishy, peculiar, and nauseous. The taste is not very marked, but is disagreeable and very slightly acrid. The grains are externally purplish-brown or black, more or less covered by a bloom, moderately brittle, the fractured surface being tolerably smooth, and whitish or purplish-white. Their specific gravity is somewhat greater than that of water, though, when thrown into this liquid they usually float at first, owing to the adherent air. The lower part of the grain is sometimes heavier than the upper (P.). When ergot is examined under the microscope, its internal part is seen to be composed of minute hexagonal or rounded cellular tissue, the cells containing from 1 to 3 globules of oil; its violet or blackish coat consists of a layer of longitudinally elongated delicate cells, and its blooms consist of sporidia. Unless kept carefully excluded from the air, it softens and swells, and becomes infected with numerous brown insects, about the size of a pin's bead, while at the same time it acquires a deep-black color and heavier odor. Its powder quickly becomes damp, and full of animalcules. It should always be used recently pulverized, or, if kept in powder, it should be in well-closed and darkened vials, and with a few lumps of camphor added. It imparts its virtues to water or alcohol; long boiling renders it inert. The best ergot is dry, and easily broken, free from insects, burns with a clear flame, and is incapable of forming a dark-blue pulp when its powder is triturated with iodine and water.

The U. S. P. requires that ergot should conform to the following description: Somewhat fusiform, obtusely triangular, usually curved, about 2 or 3 Cm. (3/4 to 1 1/4 inches) long, and 3 Mm. (1/8 inch) thick, 3-furrowed, obtuse at both ends, purplish-black, internally whitish with some purplish striae, breaking with a short fracture; odor peculiar, heavy, increased by trituration with potassium or sodium hydrate T.S.; taste oily and disagreeable. Old ergot, which breaks with a sharp snap, is almost or entirely devoid of a pinkish tinge upon the fracture, is hard and brittle between the teeth, and is comparatively odorless and tasteless, should be rejected"—(U. S. P.). The U. S. P. directs the occasional addition of a few drops of chloroform to ergot to prevent the development of insects.

Chemical Composition.—Vauquelin is generally accredited with having made the first analysis of ergot of rye, but according to his own statements, a chemical analysis of ergot had been made by Model, of Strassburg, as early as 1766 (Jour. Pharm. Chim., 1817, p. 164). Subsequent researches have brought out the most contradictory results, owing not only to the changeable character and the want of crystallizability, of the physiologically active drug constituents, but also to the tendency of various investigators to apply identical names to essentially different bodies, as well as to persistently uphold distinctions by name of substances that are essentially alike, if not identical. As a result, opinions are still divided, as to the chemical nature of the substances that constitute the active principles of ergot. Indeed, it seems as if this drug acts, as a whole, in a way that no constituent or mixture of products can do. At one time it was believed that the fatty oil which occurs in ergot in the amount of from 25 to 30 per cent, and upward, carried the medicinal properties of the drug, a belief probably due to the fact that the oil when obtained by expression or extraction with ether may hold in solution some of the active principles of ergot (ecboline). However, it was found that by abstraction, with petroleum ether, or with benzin, no ecboline will pass into the fatty oil (J. Denzel, Archiv. der Pharm., 1884, p. 314). The name ergotin has been applied to different substances by different authors. Wiggers (Prize Essay, 1831), extracted dried ergot, which had been previously deprived of its fatty oil by means of ether, with boiling alcohol, and after evaporating the solvent he treated the residue with water, which left the "ergotin" (Chemisches Centralbl., 1832, p. 276). The ergotin of Bonjean (1843), was merely an aqueous extract of ergot purified by separating out gummy and albuminous matter by means of alcohol (Amer. Jour. Pharm., Vol. XV, p. 219). W. T. Wenzell, in 1864, isolated from ergot, as he supposed, two alkaloids, ecboline and ergotine, which later investigators (e.g., Blumberg, 1878), pronounced identical. Ecboline possessed the physiological action of ergot to a powerful degree. Both alkaloids he found combined in the drug with a peculiar acid which he called ergotic acid. Besides he observed a volatile constituent, propylamine, which he pronounced identical with the volatile secaline previously observed by F. L. Winckler (1852). Walz established the presence of the volatile base, trimethylamine, which Brieger (1887) showed to be a product of decomposition of cholin, one of the constituents of ergot.

Tanret, since 1875, maintains that the active principle of ergot is represented by a crystallizable alkaloid which he called ergotinine, having the formula C35H40N4O6. Amorphous ergotinine he obtained as a by-product. Dragendorff and Podwissotzky (1876), observed the ecbolic principle of ergot to reside in two non-alkaloidal substances which they named sclerotic acid and scleromucin. The former, existing in good ergot in the amount of from 4 to 4.5 per cent, is soluble in alcohol of 80 per cent and less; the latter is soluble in alcohol of 40 per cent and less, both are soluble in water, and are difficult to obtain free from ash. If these substances are really the active principles of ergot, it becomes evident why it is not admissible to remove gummy and albuminous matter by the addition of an excess of strong alcohol. In this connection see the interesting papers by C. Lewis Diehl, and by Prof. Hallberg, in Amer. Jour. Pharm., 1881 and 1883. Dragendorff and Podwisotzky, investigating also the coloring matters of ergot, found sclererythrin, sclerojodin, scleroxanthin, and sclerocrystallin, to which they added, in 1877, picrosclerotine (a poisonous, evanescent alkaloid, perhaps identical with Tanret's ergotine, etc.), and fusco-sclerotic acid (see Jahresb. der Pharm., 1876-77).

In 1884, R. Kobert concluded from his researches that ergot contained three active principles, two of acid nature and one an alkaloid. Ergotic (ergotinic) acid, a glucosid containing nitrogen, is the principal constituent of sclerotic acid aforementioned, also of Bonjean's ergotin, and of the ergotin of Wernich, which he obtained by dialysis. It has the power of paralyzing the spinal cord, but does not produce ecbolic action. Sphacelic (sphacelinic) acid is a resin free from nitrogen, probably the main constituent of the ergotin of Wiggers. It produces gangrene. Cornutine, an exceedingly poisonous alkaloid, according to Robert is not identical with Tanret's ergotinine. Denzel (1884), however, believes it to be identical with Wenzell's ecboline which, in turn he thinks to be the same substance as Tanret's ergotinine; likewise he believes the acid principles, ergotic acid (Kobert), sclerotic acid (Dragendorff), and ergotic acid (Wenzell), to be identical. In 1894, C. C. Keller pronounced the identity of his cornutine with Tanret's ergotinine, Dragendorff's picrosclerotine, and Kobert's cornutine, on the ground that they all gave the same color reaction with concentrated sulphuric acid (a few mgr. of alkaloid first colored the acid yellowish, and after a few hours a permanent violet blue). Keller also gave directions for the assay of ergot for cornutine (see Proc. Amer. Pharm. Assoc., 1895, p. 542, and A. R. L. Dohme, ib., p. 263). Within the last few years (since 1895), Dr. C. Jacoby's researches have come to the front. In his latest experiments he strove to exclude the deleterious action of water, alkalies, and temperatures above 60° C. (140° F.), hence the substances he obtained have a just claim on our attention.

In 1895, the firm of C. F. Boehringer introduced Jacoby's spasmotin or sphacelotoxin, as a most active educt from ergot (Pharm. Centralhalle, 1895, p. 265). In 1897, however, Jacoby observed that this substance was not a simple body, but was composed of three chemically different substances, chrysotoxin, secalintoxine, and sphacelotoxin proper. The latter forms the basic principle of the others, and the relation is as follows: Sphacelotoxin + (inert) secalin = secalintoxine; sphacelotoxin + (inert) ergochrysin = chrysotoxin. Sphacelotoxin is a resin free from nitrogen, and combines the gangrenous with the uterine contractile action of ergot. Secalintoxin acts qualitatively like chrysotoxin, only the gangrenous action is more apparent on account of the greater tendency of the former to decomposition; hence the latter substance is preferred pharmacologically. In both cases sphacelotoxin, by decomposition in the organism, becomes the active principle. The mode of preparation and description of these bodies have recently appeared in print (Pharm. Centralhalle, 1898, p. 185), and may be summarized as follows: Chrysotoxin is a phenol-like body, also obtainable in crystalline form, having the composition C21H22O9. It is prepared by depriving powdered ergot of its fat by means of petroleum ether, abstracting with strictly absolute ether, evaporating the solution to a syrup and precipitating with petroleum ether. By redissolving in ether and fractionally precipitating with petroleum ether, pure chrysotoxin is obtained. This substance is insoluble in water, diluted acids, and petroleum ether; soluble in ether, chloroform, alcohol, benzene, glacial acetic acid, etc. Caustic alkalies form golden-yellow solutions that are altered by warming. Prolonged contact with excess of alkali converts it into inert ergochrysinic acid, precipitable by acids. This is probably a constituent of Kobert's sphacelinic acid. Chrysotoxin is administered in the form of its sodium compound.

Secalintoxine is a pronounced alkaloid contained in the first fractions in the preparation of chrysotoxin. The impure chrysotoxin is dissolved in ether, the alkaloid shaken out with diluted acetic acid, and precipitated by means of sodium carbonate. In pure form it is soluble in alcohol, acetic ether, chloroform, benzene, less soluble in ether, little soluble in water and weak alkalies, and insoluble in benzin and petroleum ether. With concentrated sulphuric acid it gave Keller's cornutine reaction, without being identical with this substance, as both differ markedly in their physiological actions. Evaporated on the water-bath repeatedly with alcohol and concentrated hydrochloric acid, traces of the alkaloid leave a beautiful violet-colored residue. Ergochrysin is a yellow, inert coloring matter, soluble in water and in glacial acetic acid. Secalin is obtainable, in crystals of several millimeters in length, from secalintoxin. It is a pronounced alkaloid, yet stated to be not identical with Kobert's cornutine, nor Tanret's ergotinine, as it does not possess the contractile activity of the latter. It gives the color reaction of secalintoxine in a more pronounced degree, and exhibits a beautifully blue fluorescence in alcoholic solution. It has the formula C29H55N6O14. Sphacelotoxin is obtained as a yellow resinous mass which soon turns greenish, by precipitating with petroleum ether an ethereal solution of secalintoxine. Crystals of secalin are also formed. Decomposition of secalintoxine into its components, secalin and sphacelotoxin, is best effected by means of lime. It contains traces only of nitrogen and gives but faintly the secaline reaction above mentioned.

Other Constituents of Ergot.—Among these may be mentioned vegetable albumen (Wiggers, 1831); ash (5 per cent, especially rich in phosphates); acetic, lactic, and formic acids, probably occurring in decomposed ergot only; cholaterin, recorded by Schoonbrodt (1863), though Tanret (1889) considers it peculiar to ergot, naming it ergosterin. It is probably identical with the substance that Wiggers, in 1831, named cerin (see Wiggers, Jahresb. der Pharm., 1869, p. 25). Leucin (amidocapronic acid) mannit, and reducing sugar, are also present in ergot. Wiggers observed a sugar peculiar to ergot, which was non-reducing and not readily fermentable. It was called mycose by Mitscherlich, and thought to be identical with trehalose by Muntz. Mucilage is present in ergot in appreciable amount. A peculiar, crystallizable body, vernin (C16H20N8O8+3H2O), discovered by E. Schulze and Von Planta, and found to occur in various plants, associated with asparagin, has also been observed in ergot (see Jahresb. der Pharm., 1886, p. 15).

In conclusion it maybe said that notwithstanding the voluminous literature on this subject and the patient work devoted to the chemistry of ergot, much remains yet to be done when it comes to affiliating the chemical record and the therapeutical constituents. It is evident, as before stated, that in therapy such preparations as liquids containing natural groups of constituents, made by methods that do not use heroic chemistry, are as yet the logical preparations to be used by conservative physicians.

Detection of Ergot in Flour, Bread, etc.—Ergot may be detected when mixed with farinaceous substances, by the following method of M. Wittstein: Mix the suspected substance with a little water in a test tube, and cover with a layer of solution of caustic potash—if ergot be present, trimethylamine is disengaged, which has an unmistakable odor of fish-brine; the application of heat favors the development of this substance, but likewise quickly dissipates it. By simply mixing the bread or flour containing ergot with milk of lime and allowing it to stand for some time, the odor just described becomes apparent.

Flückiger (Pharmacognosie, 3d ed., 1891), favors Hilger's color test, which is carried out as follows: Shake 10 grammes of the flour suspected of containing ergot with 20 grammes of ether and 10 drops of diluted sulphuric acid (sp. g. 1.11), allow to stand for 6 hours, filter, and wash with sufficient ether to collect 20 grammes of filtrate. Add 10 drops of a solution of sodium bicarbonate saturated in the cold, and shake; the red violet coloring matter, due to the presence of ergot, will then appear in the lower (aqueous) layer. The test gives good results even with 1 gramme of flour containing only 1 per cent of ergot. The color reaction remains permanent for weeks. For further chemical and some microscopical tests, see Flückiger. To distinguish fresh from old ergot, Koster (Amer. Jour. Pharm., 1885, p. 241), recommends macerating for some time 2 Gm. of the powder with 5 Cc. of ether. The resulting solution is colorless if the ergot is fresh, but yellowish if it is old.

Action, Medical Uses, and Dosage.—I. ERGOT. Ergot exerts a remarkable effect on the human system, more especially when its use has been persevered in for some time. Its most serious influences are those occasioned by the continued use of affected rye as food, and which are manifested by certain symptoms termed ergotism, which assumes two types—convulsive ergotism and gangrenous. These two forms do not present well-defined pathological differences, though they differ in termination. The first form is characterized by weariness, giddiness, muscular contraction, formication, dimness of sight, voracious appetite, loss of sensibility, yellow countenance, convulsions, and death. The second is likewise accompanied by formication, voracious appetite, insensibility, and gangrene (either moist or dry) of the extremities, with dropping off of the toes. In doses of from 30 to 60 grains, and especially when the stomach is in an irritable condition, it frequently causes vomiting and nausea. When given in large doses, it is apt to affect the cerebro-spinal system, as known by restlessness, heaviness of the head, headache, vertigo, enlarged pupils, tinnitus aurium, and other symptoms of narcotism, with depressed heart and respiratory action, and gastro-intestinal irritation with sudden nausea and vomiting. These effects have been termed acute ergotism. It frequently lessens the action of the heart and arteries, though sometimes this is increased, with febrile symptoms, especially during parturition. A single dose, varying from 2 to 8 drachms, has occasioned vomiting, colic, pains, and headache; single doses of 20 to 40 grains have no great influence under ordinary circumstances.

The exact physiological action of ergot is still a matter of investigation, but the view chiefly held is that it acts mainly upon the vascular and nervous systems, as follows: Microscopic examinations of the retina, spinal and cerebral meninges, and of the frog's foot, show its power to contract the arterioles. Ergot depresses the heart and dilates the veins, the effect of which is a deficient supply of blood to the arteries, causing an inactive contraction or in reality an arterial collapse. To this result is due its effects upon the nervous structures, causing an anemia of the cerebro-spinal axis and ganglionic centers and of the organic muscular structures. The primary effect of ergot on the circulation is a fall in blood pressure, but its ultimate effect is to induce a rise in blood pressure.

The effects of ergot are not fully produced by the many so-called active principles of ergot. The action of ergotin, however, most closely resembles that of the parent drug. It has been shown by Köhler that Wiggers' ergotin has no effect upon the circulatory apparatus, but may induce intestinal cramps and violent gastro-intestinal inflammation, while Bonjean's ergotin is free from such effects, and slows the heart, contracts the arterioles, lessens temperature, and diminishes reflex phenomena. In very large doses the latter paralyzes the heart, and the muscular tissues fail to respond to the galvanic current. Ergotic acid is thought to be the active ingredient of Bonjean's ergotin. It must be used hypodermatically, as it is destroyed in the stomach. It undoubtedly has hemostatic power, but does not cause uterine contractions. Sphacelic acid and cornutine (chiefly the latter), are thought to be the effective agents in the induction of uterine contractions, and to the former have been attributed the gangrenous effects of ergot.

Ergot does not readily kill in a single large dose, fatal effects, when occurring, being developed from the long-continued use of small doses. A teaspoonful of tincture of ergot, taken 3 times a day for 11 weeks, was alleged to have caused the death of a woman 3 months pregnant. The only post-mortem features were inflammatory patches on the gastric mucous membrane (Taylor, Med. Juris., p. 622). The treatment for acute ergotism is chiefly symptomatic. Cardiac stimulants, as caffeine, coffee, etc., or amyl nitrite by inhalation, may be employed. The hot bath and dry heat increase the effects of the medicinal treatment.

Medicinally, ergot is chiefly used on account of its power of promoting uterine contraction in languid natural labors. When thus employed, it produces a strong, continued, and, as it were, spasmodic contraction of the uterus, seldom permitting any relaxation until the child is born, and often continuing for some minutes after. The contractions and pains caused by ergot are distinguished from those of natural labor by their continuance; scarcely any interval can be perceived between them, but a sensation is experienced of one continued forcing effort. Sometimes ergot causes no unpleasant effects on the system; and likewise fails to excite uterine contractions, which will be found the case with other parturient agents. The causes of these failures are not known, being merely conjectural. It is said that ergot poisons the child and causes its death. This may, probably, sometimes be the case, but I am induced to believe that the fatality more generally ensues in consequence of the long-continued and constant pressure of the contracted organ upon the cord and fetus, causing its utero-fetal circulation to cease, and thus destroying it by asphyxia (J. King). In support of the view that ergot probably does not directly operate in a poisonous manner upon the child, may be cited the testimony of Uvedale West (see Taylor, Med. Juris., p. 521), who administered ergot during the births of 173 children, only 5 of whom were still-born. In a state of pregnancy, ergot will undoubtedly occasion abortion, though it sometimes fails here likewise. However, many contend that it is incapable of producing abortion, but that it is effectual only after uterine contractions have already commenced—that, while it is an ecbolic it is not an abortifacient. It also influences the non-gravid uterus, producing painful contractions or bearing-down pains, and on this account has been useful in checking menorrhagia, uterine hemorrhage, and in expelling polypus masses.

As a parturient, its use should always be avoided, if possible, in first labors, nor is it to be used in the early stage of normal labor. In our opinion there are but two chief indications for the use of ergot in labor, and these are uterine inertia and alarming hemorrhage, and as the latter is most frequently post-partum, a full hypodermatic injection of Lloyd's ergot should be given as soon as the head is born, when hemorrhage threatens. The conditions for safety and success are that the labor be somewhat advanced, the mouth of the womb being moderately dilated, that no mechanical obstruction to delivery exists, as deformity of the pelvis, rigidity of the os uteri, mal-presentation, or, disparity of the size of the child to the parts of the mother, and more especially that the only cause of the slow progress of labor is insufficiency of the uterine contractions in point of force or frequency. One or 2 drachms of the powder may be stirred in 4 fluid ounces of hot water, and, when sufficiently cool, may be given in teaspoonful doses every 10 minutes until labor pains are induced; usually in 15 or 20 minutes the labor pains increase in force and frequency, and gradually become continuous, and effect the expulsion of the child within an hour. A good fluid extract of ergot, or Lloyd's ergot (non-alcoholic), are equally as efficient as crude ergot. To simply increase labor pains already existing not more than 5 drops, every 20 or 30 minutes are required; when speedy expulsion is sought, the dose should be 1 fluid drachm, by mouth or hypodermatically, every half hour or hour. When to be used simply to facilitate labor which is slowly progressing, the following was advised by Prof. J. M. Scudder: Rx Specific ergot, flℨi; water, fl℥ij. Teaspoonful every half hour or hour. Such doses exert a stimulant influence, strengthen uterine contractions, and aid dilatation of the os uteri. The cases usually calling for these doses are those with feeble circulation, puffiness of the face, and oedematous feet. If the os uteri be rigid, thick, and doughy, lobelia should be associated with it.

In cases where the child is dead, and circumstances require prompt delivery, as, where the patient is greatly exhausted, or where the system becomes very irritable, etc., ergot may be administered, provided there be no obstruction to a safe delivery. It may likewise be administered to facilitate abortion when it has once commenced, as well as to check uterine hemorrhage in the gravid or non-gravid state. It may likewise be given for promoting the expulsion of a mole, hydatids, a clot of blood, or other uterine contents, when the womb has once begun to act. The practice of administering ergot to cause the expulsion of the placenta is not to be commended, for some of the worst cases of placental retention, especially when the placenta is adherent, have been caused by the constant contraction produced, thus imprisoning the secundines until septic consequences have ensued. It is far better to remove the placenta by mechanical means, and then to use ergot in case hemorrhage of any consequence follows. Neither do we approve of the custom of administering to every parturient, at the close of labor, a dose of ergot. If there is a history of hemorrhage at or after previous confinements, or present indications of such an accident, or there is uterine inertia, such a procedure is permissible and often imperatively demanded. But where no hemorrhage occurs the imprisonment of placental tissues and other debris, as well as the increased severity of the after-pains that usually occur, are a sufficient protest in themselves against the indiscriminate employment of a remedy so productive of harm as ergot. Ergot should never be administered unless there be present or impending complications imperatively demanding its exhibition.

Ergot is an admirable remedy for hemorrhage, post-partum or otherwise. For this purpose ergotin (see below) is also frequently employed. It is useful in epistaxis, hematemesis, hematuria menorrhagia, from large, spongy, subinvoluted womb, especially in scrofulous subjects, and in intestinal hemorrhage. It is sometimes useful in the hemorrhages accompanying typhoid fever. It is particularly useful, combined with appropriate constitutional treatment, in a hemorrhagic diathesis. It has given good results in hemorrhagica purpura. Dysentery, with bloody evacuations, has been relieved by it, and given internally or applied by suppository, it has given relief in hemorrhoids. It forms an excellent adjunct in the treatment of passive hemoptysis, the following having proven very serviceable in our hands: Rx Specific ergot, tincture of cinnamon (oil), and specific lycopus, aa flℨij. Mix. Sig. Dose, 20 drops, in water, every hour until relieved. If the hemorrhage be active, 60 drops may be given every half hour. Prof. Locke advises (Syllab. of Mat. Med., p. 386), the following at one dose, to be repeated every half hour if necessary: Rx Specific ergot, gtt. x; ipecac, grs. ss; gallic acid, grs. ij. Mix. He advises the same in post-partum hemorrhage, and in intestinal hemorrhage from typhoid fever. The action of ergot is enhanced by the conjoint administration of specific geranium, gallic acid, hamamelis, cinnamon, or lycopus. For the hemorrhage from cancerous growths, Prof. Locke advises the dusting of the surface with finely-powdered ergot and covering with a cloth wrung from a weak phenol solution. Ergot has given good results in aneurism, especially when small, and is accredited very serviceable in dilated heart, without lesions of the valves.

Ergot has a decided action of the muscular fibers of the bladder. Large doses may contract the fibers so as to cause retention of urine. In incontinence of urine and other bladder affections due to relaxation of the sphincter vesicae, specific ergot in doses of from 10 to 30 drops in water, render good service. It may be combined with buchu as follows: Rx Specific ergot, fl℥ss; specific buchu, fl℥j; simple syrup, fl℥ijss. Mix. Sig. One teaspoonful 3 or 4 times a day (Locke). Cystic paralysis is sometimes relieved by ergot, and particularly when due to overdistension of the bladder. Amenorrhoea, due to relaxed uterine tissues, or to congestive conditions, is relieved by specific ergot in small doses, and it is useful in leucorrhoea, due to similar causes. It is also a good remedy in the congestive form of dysmenorrhoea; here it may be associated with other appropriate remedies. As before stated, it is doubted by many whether ergot will excite uterine contractions in any instance, unless a natural movement toward such action has commenced, but, as previously remarked, there is no doubt of its influence upon the womb at other times than that of parturition. There is abundant evidence that small doses of ergot have prevented abortion. For uterine subinvolution ergot is one of the most positive of remedies. In small doses it has been recommended in painful dysmenorrhoea, where membraneous shreds pass off. Sometimes it has proved advantageous in fever and ague, but is rarely used for this purpose. The dose should range from 5 to 10 or 15 grains, or an equivalent amount of specific ergot, 3 times a day, but its use should not be persisted in too long, on account of its tendency to cause dangerous symptoms. It is not without value in spermatorrhoea, gonorrhoea, and enlarged prostate. Small doses relieve false pains associated with fullness and uneasiness of the genitalia, and oedema with dullness, hebetude, and tendency to coma (Scudder). In skin diseases it has had a limited use in erythema, urticaria, prurigo, acne rosacea (locally and internally) and incipient furuncles (locally). Locally, seborrhoea is well treated with the oil of ergot.

Ergot is valuable in certain forms of nervous diseases. According to Dr. Brown-Sequard, ergot diminishes the blood in the spinal cord, by causing a contraction of its blood vessels; dilates the pupil; acts more especially on the fibers of the womb and of the bladder and urethra, and appears to exert a more powerful influence on the inferior portion of the spinal cord. He suggested that it be used in the same forms of paralysis and disease of the spinal cord, as belladonna. Bonjean's purified extract (ergotin), in the dose of from 2 to 10 grains, 2 or 3 times a day, is often employed in the spinal and cerebellar lesions resulting from masturbation and sexual excesses. The nervous disorders to which ergot is adapted are those of a hyperemic or congestive character, and it is always contraindicated by anemia. It has been found particularly useful in congestive headaches, and particularly migraine, with flushed face, full pulse, and suffused eyes. Its action upon the circulation closely resembles that of belladonna, and the general indications are much the same. In any trouble, "with enfeebled capillary circulation with tendency to congestion, especially of the nerve-centers, ergot may be prescribed with advantage" (Scudder). The indications are dull, full eyes, with pupillary dilatation, fullness of the veins, slow pulse, sighing respiration and tendency to coma. With these indications it has been found very serviceable in paraplegia, cerebral hyperemia, chronic mania, recurrent mania, epileptic mania, acute myelitis, spinal congestion, etc. In mental disorders, dependent on intracranial congestion or obstruction, with bleeding from the nose, dizziness, hebetude, or headache, and tinnitus, due to intracranial miliary aneurisms, ergot appears to render efficient service.

Fluid extract of ergot, or a paste of ergotin, locally applied, has been of value, in follicular pharyngitis. Foltz (see Webster's Dynamical Therapeutics, pp. 577 and 621) is a strong advocate of the use of ergot in diseases of the eye. Thus, besides the common use of the drug for conjunctival congestion and for the hemorrhage following enucleation of the globe, he advises it in the following conditions: Superficial conjunctivitis and keratitis, in follicular conjunctivitis (claiming it better than any other drug), ophthalmia neonatorum, incipient trachona, plychtenulae, pannus, with great vascularization, and pinguecula. He declares it of service in episcleritis or involvement of the deeper structures of the eye. As a collyrium, he advises Lloyd's ergot gtt. xv to xxx to sufficient water to make 1/2 fluid ounce. Foltz further recommends full doses (Lloyd's ergot, 1/2 to 1 fluid drachm) in relaxed or congested retinal vessels, hyperemia of the optic disc, and hemorrhage into the vitreous humor. In combination with boric acid be employs ergot locally by insufflation in purulent otitis media, with little discharge and a turgid tympanic membrane: Rx Boric acid, ℨj; fluid extract of ergot (Squibb's), fl℥ss. Mix. Triturate until dry. Ergot has given relief in exophthalmic goitre. Ergot and ergotin, both locally and internally, have been very effectual in reducing nasal hypertrophies.

II. ERGOTIN.—The facility with which solution of ergotin may be employed in hypodermatic injections, its rapidity of action, and its efficiency, render it superior to any other mode of administration. Yvon's solution (see Liq. Ergota) is especially available. (Bonjean's ergotin may be used for the same purposes.) When it is properly made it is innocuous, and occasions neither pain nor inflammation. It as been successfully employed in post-partum hemorrhages, the only unpleasant symptom observed being a sudden headache with vertigo, nausea, and syncope, which passes off in a few minutes by placing the patient in a horizontal position—but no symptoms resembling those of poisoning. Its effects are better manifested in passive hemorrhages due to inertia or atony of the uterus. The use of this solution by subcutaneous injections has likewise been found efficient in excessive menorrhagia, epistaxis, hemoptysis, and other profuse and obstinate hemorrhages, as gastrorrhagia, enterorrhagia, cerebral hemorrhage, and in secondary hemorrhages following surgical operations. They have likewise been of service in uterine fibroma; the soft, vascular, hemorrhagic tumors, of rapid development during the sexual life, being more readily influenced by the ergotin; while, on the contrary, the long-standing, hard, voluminous, stationary tumors, which have formed adhesions or undergone fatty degeneration, especially with females who have reached or passed the critical age, are hardly, if at all, influenced by it. Subcutaneous injections of ergotin have also proved effective in prostatic enlargement, goitre, prolapsus of the rectum, purpura hemorrhagica, internal aneurism, diabetes insipidus, paraplegia, paralysis of the bladder, and enlargement of the spleen, especially when the result of malarial influences. Ergotin has a special influence upon the fibers of the smooth muscles. M. Bernard, who has given considerable attention to the subject, sums up his conclusions as follows: Subcutaneous injections of ergotin act upon hemorrhages by causing contraction of the smooth fibers of the blood-vessels, or of those of the organs enclosing them. They appear to act locally at the point where the ergotin is in contact with the tissues, but this action does not appear to be independent of the influence of the nervous system. Contraction of the smooth vascular fibers acts especially by modifying the tension of the blood; contraction of the fibers of the organs containing them acts especially by effacing their caliber—compressing them. Injections of ergotin appear to act efficiently, even in hemorrhages of organs deprived of smooth fibers, or presenting few of them in their structure, as in gastro-intestinal hemorrhages, hemoptysis, and epistaxis. Hemorrhages of organs in which the smooth fibers predominate; that is to say metrorrhagia, are almost constantly cured or ameliorated by injections of ergotin. Their influence is especially manifest in the gravid condition of the uterus, or in conditions approaching it, as moles and intra-uterine fibromae. It is likewise very energetic when the muscular fiber of the organ is healthy, even when a portion of the organ is already destroyed, as by cancer. In cases of metritis, and especially of fungous growths, their influence is about null. When carefully made, and a properly prepared solution is employed, no serious symptoms result. Bartholow employed successfully the hypodermatic injection of ergotin (2 grs.) for the radical cure of varicocele. Seldom more than two injections were necessary. The operation is very painful, and care must be exercised not to puncture the veins, the solution simply being injected among the vessels. Varicosities have been similarly treated.

The dose of ergotin, by hypodermatic injection, varies according to circumstances, from 1/6 of a grain to 5 grains per day. Some practitioners have even exceeded this quantity, using from 3 to 10 grains daily. The quantity of Yvon's solution of ergotin will, therefore, be from 1/6 of a minim to 5 minims per day. The fractions of a minim may be made by adding water to the solution, thus: To obtain 1/6 of a minim, add 1 minim of the solution to 23 minims of distilled water; 4 minims of this mixture will equal the 1/6 of a minim of solution. The injections should be made in the neighborhood of the diseased parts, and be repeated, according to the circumstances, every 2, 3, or 4 days. In uterine myoma, M. Gerard prefers to inject directly into the uterine tissue. In profuse hemorrhages, from 3 to 5 or 10 minims may be used at a time, and, if necessary, may be repeated every 4, 8, or 12 hours, according to the urgency of the case, and the effect of the agent. In enlarged spleen, from 1 to 5 grains of ergotin have been injected daily.

The dose of ergot depends upon the conditions for which it is to be used. For rapid expulsive purposes in labor, or for active hemorrhage, the dose ranges from 5 to 30 grains, or from 5 drops to 2 fluid drachms of the fluid extract, or 5 to 60 drops of specific ergot or Lloyd's ergot. Lloyd's ergot, being non-alcoholic and representing grain for minim, is an excellent preparation for hypodermatic use. For specific purposes the dose of good fluid preparations of ergot ranges from 1 to 5 drops, seldom exceeding 10 drops. Bonjean's ergotin may be given internally to the extent of 10 grains, half that quantity being about the limit for hypodermatic use. The large doses above given are seldom required, about 1/3 the stated amount being usually administered. Tanret's ergotinine may be used subcutaneously in doses not exceeding 1/60 grain.

Specific Indications and Uses.—Uterine inertia during labor, when conditions are otherwise favorable for a safe delivery; hemorrhage due to atony, with weak pulse, cold surface, and dilated (sometimes contracted) pupils; post-partum hemorrhage (large doses); to expel loosened foreign particles from the womb; congestion or hyperemia of any part; venous fullness; mental apathy; dullness, hebetude, and tendency to coma; fullness and uneasiness of genitalia, with oedema; congestive headache; hemiplegia and paraplegia, with hyperemia or congestion; feeble circulation; hyperemic or congestive eye and ear disorders; otorrhoea, discharge slight and membrane turgid.

Other Forms of Ergot.—ERGOT OF WHEAT. This form of ergot is hand-picked in France and Italy from the wheat intended for the manufacture of vermicelli, pastes, etc. The ergots are thicker and shorter than those from rye, are said to retain their good qualities longer, and to be free from the deleterious action of the latter.

ERGOT OF OATS.—More slender than the ergot of rye. Sometimes collected to mix with the latter, or to be sold per see (Le Perdriel, Pharmacographia).

ERGOT OF DISS.—From Arundo Ampelodesmos, Cirillo. A reed grass of North Africa. It was first detected in 1842 by M. Durien de Maisonneuve, in Algeria (E. M. Holmes, Amer. Jour. Pharm., 1886, p. 203). It is from 1 to 3 inches long, about 1/10 inch broad, curved, or if large, spirally twisted. Resembles ergot of rye in structure, and according to Lallemand, is said to possess double the activity of that product.

[image:16154 align=left hspace=1]Ergot-yielding Plant.—RYE. The grain of Secale cereale, Linné. Nat. Ord.—Gramineae. Rye has a stem 4 to 6 feet high, hairy beneath the spike, in a wild state seldom over a foot high. Leaves lance-linear, rough-edged, and rough above, glaucous; lower ones, together with their sheaths, covered with a soft down. Rachis bearded on each side with white hairs. Glumes subulate, ciliated, scabrous, shorter than the florets, taken together with their awns. Outer paleae folded up, keeled, tri-nerved, with very long awns; the 2 nerves and awns very rough. Stamens 3. Ovary pyriform, pilose. Stigmas 2 (L.—W.). The native country of rye is not positively known, though supposed to have originated about the Caucasus; at present day it is considerably cultivated among civilized nations. Ground into fine flour it is used as an article of diet in the form of bread or mush. Rye bread is not so light-colored, nor so readily digested as wheat bread. According to Einhof, the grain consists of about 6 1/2 per cent of meal, the balance being husk or bran, nearly 2 1/2 per cent, and moisture. The meal consists of starch 61.07, gum 11.09, gluten 9.48, albumen 3.28, saccharine matter 3.28, husk, salts, acid, etc. (P.). Rye is frequently attacked by the parasite Claviceps purpurea (Fries) Tulasne, the result being the production of the fungus, ergot.

Rye-bread, or rye-mush, is laxative, especially to those unaccustomed to its use, and is sometimes taken to obviate costiveness. The dry flour allays the heat and itching of erysipelas and other affections of the skin when applied upon the affected parts. In the form of poultice it is often applied to discuss tumors or swellings, or to hasten their suppuration, when far advanced.

Green rye, when from 6 to 10 inches high, made into a salve by simmering in fresh cream, I have known to cure several most inveterate cases of tinea capitis; to be applied to the scalp twice a day (King).

King's American Dispensatory, 1898, was written by Harvey Wickes Felter, M.D., and John Uri Lloyd, Phr. M., Ph. D.

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