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Ergota, B. P. Ergot.

Botanical name:

Related entries: Ergotinine - Ergotoxine - Ergotoxine phosphate

Ergot (ergot of rye) consists of the dried sclerotium of a fungus, Claviceps purpurea, Tulasne (N.O. Pyrenomycetes), the spores of which have developed in the ovary of Secale cereale, Linn. (N.O. Gramineae). It is also official in the U.S.P. The drug is imported chiefly from Spain and Russia. It is sometimes collected by picking from the grain by hand, but is more often separated by sifting. Spanish and Russian are the chief commercial varieties, but others (German, Austrian, Swiss, Swedish) are known. Spanish ergot is larger than Russian, and contains less ergotinine (about 0.20 as compared with 0.25 per cent.). Ergot can also be obtained from wheat and other plants belonging to the Gramineae, but ergot of rye, which is alone official, is distinguished by its size. The grains of ergot are dark violet-black in colour, 1 to 4 centimetres long, slender, curved, and tapering towards both ends, somewhat triangular in transverse section. They are longitudinally furrowed, especially on the concave side, break with a short fracture, and are whitish within. The odour and taste are characteristic and disagreeable. Ergot deteriorates rapidly when kept in open vessels and in a damp atmosphere; it should, therefore, be thoroughly dried and preserved in well-closed vessels. The Brussels Conference agreed that ergot should not be more than one year old and should be preserved entire.

Constituents.—Ergot appears to owe its activity to decomposition products of proteins produced by putrefaction. One constituent of the drug is the complex, physiologically active alkaloid ergotoxine or hydroergotinine, C35H31N5O6, also known as amorphous ergotinine and, when formerly obtained in an impure state, as cornutine or ecboline; it is the hydrate of the comparatively inert, crystalline base ergotinine, or ergotine, C35H39N5O5. which also exists in ergot, and into which ergotoxine can be converted by boiling it with acetic anhydride or methyl alcohol, when loss of a molecule of water occurs. Other physiologically active constituents of ergot are simpler bases, derived from amino-acids by the elimination of carbon dioxide, generally formed in putrefaction and found in ergot extracts. Of these, the most important are ergotamine, ergotidine, and agmatine. Ergotamine or p-hydroxyphenylethylamine, C8H11NO, also known under the trade-name Tyramine, is produced by splitting off carbon dioxide from tyrosine, and is closely related to adrenine and hordenine; ergotidine, (4-β-aminoethylglyoxaline or β-iminazolylethylamine, C5H9N3), is produced from histidine in the same way that ergotamine is produced from tyrosine. and agmatine, C5H15N4, is a similar derivative of arginine. The characteristic gangrene of the cock's comb and other toxic symptoms of ergot are caused by ergotoxine, which also produces a rise of arterial blood pressure, causing contraction of the arteries, uterus, and some other plain muscular organs; ergotamine also causes rise of blood pressure and produces contraction of the cat's uterus in the pregnant condition, while ergotidine causes a fall of blood pressure, but has a marked action on plain muscle, the uterus in particular being stimulated to intense contraction by minute doses; ergotidine and agmatine both produce contraction of the isolated uterus of the non-pregnant cat. A crystalline alkaloid named ergothioneine, C9H15N3O2S,2H2O, said to be obtained from ergot, is described as soluble in water, but only sparingly soluble in alcohol. It is roughly correct, in view of our present incomplete knowledge, to say that the gangrene-producing substance in ergot is ergotoxine, but that this substance is not of much therapeutical significance, since it is almost absent from the preparation of ergot most generally used, the liquid- extract. The blood pressure raising substance in the extract is ergotamine or p-hydroxyphenylethylamine, but clinical experiments seem to show that this is of little value on the uterus, far inferior to the crude liquid extract. No clinical experiments with ergotidine are yet recorded, but it seems probable that this may be the long sought for uterine stimulant. Many other substances extracted from ergot, and to which definite names have been given, are impure bases or mixtures. Thus, ergotinine in an impure state has been named picrosclerotine, sclerocrystalline, and secaline; clavin is an inert mixture of leucine and other amino-acids; sphacelinic acid or sphacelotoxin is probably impure ergotoxine, and sclerotinic or ergotinic acid impure ergotidine. Various crystalline and amorphous colouring matters have also been extracted from ergot, including ergoxanthein, scleroxanthein, fuscosclerotinic acid, scleroerythrin, and scleroiodin. Ergot contains about 30 per cent. of fixed oil, which can be extracted by petroleum spirit, a phytosterol (ergosterol), being simultaneously removed. The drug also contains trehalose and mannite; it yields about 3 per cent. of ash.

Action and Uses.—Ergot stimulates plain muscle, directly or indirectly, throughout the body. The peripheral arterioles undergo a prolonged constriction and cause a considerable increase of blood pressure in man., The heart beats more vigorously, its systole is more complete and its output is considerably increased. The action of ergot on the uterus is like that on other plain muscle; it augments the contraction of the fibres, and produces a more active peristalsis. It therefore has an emmenagogue effect in the non-gravid condition and an ecbolic effect on the gravid uterus. Ergot is employed, almost entirely, to excite uterine contractions. It is thus largely used to check uterine haemorrhage, and is especially valuable in the third stage of labour. Ergot is also employed, though rarely, to arrest internal haemorrhage. For all haemorrhage, other than uterine, it may do positive harm by raising blood pressure. This is especially the case in haemorrhage from the cerebral and pulmonary vessels, because these vessels are so poorly provided with vaso-motor nerves, that not only is the pressure raised in them by ergot, but they are opened up and made to dilate by the systemic constriction. It is sometimes of service in epistaxis and in night-sweats. Two types of epidemic ergotism, caused by the prolonged use of ergotised rye bread, have been described, but are rarely or never found together. There is a gangrenous form which is characterised by agonising pain in the extremities followed by dry gangrene of the peripheral parts of the body (ergotoxine action); and a second or nervous type of epidemic which is much more rare and is characterised by paroxysmal epileptiform convulsions. Modern ergot does not seem to contain a body having this type of action. No method of standardising ergot by chemical means is at present known; but, as many specimens of ergot and of its galenical preparations are physiologically inert, it is necessary that their activity should be ascertained by physiological experiment. This may be achieved by observation of the power of the preparation to raise blood pressure through vaso-constriction and contract the uterus, or indirectly by observing the effects of such vaso-constriction in causing gangrene of certain peripheral portions of the body. The gangrene so produced is especially manifest in the comb and wattles of fowls, and this very rough test is sometimes employed to show the activity of the ergot preparations under examination. Ergot is usually administered in the form of extract (ergotin), liquid extract, infusion, or ammoniated tincture. Extractum Ergotae requires evaporation with the addition of a little powdered liquorice to make a firm pill. Extractum Ergotae Liquidum and Infusum Ergotae are compatible with alkalies; mineral acids precipitate some colouring matter. The liquid extract is most largely used, although the infusion is the more active preparation when made from well dried and carefully stored ergot. Tincture of ferric chloride precipitates the liquid extract and the infusion of ergot; this may be avoided by the addition of a few grains of citric acid. Ammonio-citrate of iron is more compatible with ergot preparations. Injectio Ergotae Hypodermica should be freshly prepared, and its action is then powerful and prompt; separate doses may be enclosed in sterilised sealed glass capsules to avoid contamination of the bulk of the solution..

Dose of the fresh powder.—12 to 40 decigrams (20 to 60 grains).


Extractum Ergotae B.P.—EXTRACT OF ERGOT. Syn.—Ergotin.
Ergot, in No. 40 powder, 100; diluted hydrochloric acid, 4.7; sodium carbonate, 2; alcohol 60 per cent.), a sufficient quantity; distilled water, a sufficient quantity. Add 50 of the alcohol to the powdered drug, pack in a percolator, exhaust by percolation with more alcohol, and evaporate the percolate to 25; then dilute the liquid with an equal volume of distilled water, cool, and filter, washing the residue with a little water. To the filtrate add the acid and set aside for twenty-four hours, then filter, wash the residue with water until the washings cease to give an acid reaction, and add the washings to the filtrate; finally add the sodium carbonate, and evaporate to a soft extract. This preparation tends to produce a mild but prolonged ergot effect, and is preferred to Bonjean's ergotin, which is prepared by exhausting the drug with water, and purifying with alcohol before evaporating. Extract of ergot is commonly given in pills, stiffened with a little powdered liquorice or althaea. If prescribed with other soft extracts, the mass may be evaporated over a water-bath. Capsules of extract of ergot are prepared containing usually 18 centigrams (3 grains in each). Extract of ergot is used in the preparation of solutions for hypodermic use (see Injectio Ergotae Hypodermica). This extract is preferred by some practitioners to Extractum Ergotae Liquidum, and for use in the form of mixture it may be dissolved in water with a little glycerin, and spirit of chloroform added as a flavouring and preservative agent. When ordered in capsules, extract of ergot should be evaporated to about three-fourths its bulk, and then made up to its original volume by the addition of soft paraffin. Dose.—1 to 5 decigrams (2 to 8 grains).
Extractum Ergoti, P.I.—EXTRACT OF ERGOT, P.I.
A watery extract is first prepared and made up with alcohol (60 per cent.).
Extractum Ergotae, U.S.P.—EXTRACT OF ERGOT, U.S.P.
Ergot, 800; hydrochloric acid (10 per cent.), 40; monohydrated sodium carbonate, 6.8; glycerin, by weight, 10; alcohol (95 per cent.), 800; distilled water, 320. The ergot is exhausted by percolation with alcohol and water mixed in the proportions given above, the percolate evaporated to 200, by weight, at a temperature not exceeding 50°; 200 of distilled water is then added; the liquid cooled and filtered; the hydrochloric acid is added, and the mixture set aside for twenty-four hours, then filtered and washed until the washings are free from acid; the sodium carbonate is added to the combined washings and filtrate and the liquid evaporated to 120 by weight; the glycerin is then added and the evaporation continued until the preparation weighs 100. Average dose.—2.5 decigrams (4 grains).
Extractum Ergotae Ammoniatum Liquidum, B.P.C.—AMMONIATED LIQUID EXTRACT OF ERGOT. 1 in 1.
This preparation is about four times the strength of the official ammoniated tincture of ergot; it is not, however, very active, and there is reason to believe that the ammonia slowly destroys the active principle of the drug. Ammoniated preparations of ergot should not be prescribed with salts of iron. Dose.—1/2 to 2 mils (10 to 30 minims).
Extractum Ergotae Liquidum, B.P.—LIQUID EXTRACT OF ERGOT. Syn.—Liquor Ergotae.
Ergot, crushed, 100; distilled water, 750; alcohol, 37.5. Mix the drug with 500 of the water, allow to digest for twelve hours, remove the liquid, and repeat the process with the rest of the water; then press, strain the mixed liquid, evaporate to 70, cool, add the alcohol, set aside for an hour, and filter. The product should measure 100. It has been suggested that this extract should be made by percolation instead of maceration. A more active extract still is obtained by percolation with a semi-alcoholic menstruum. The liquid extract of ergot is the most commonly used, though it is perhaps not the most active or permanent preparation of ergot. When it is prescribed with ferric chloride, a few grains of citric acid should also be ordered to avoid precipitation. The nauseous taste of ergot maybe covered with tincture of orange and spirit of chloroform or cinnamon water. Dose.—1/2 to 2 mils (10 to 30 minims).
Extractum Ergoti Liquidum, P.I.—LIQUID EXTRACT OF ERGOT, P.I.
Strength, 100 per cent.
Fluidextractum Ergotae, U.S.P.—FLUIDEXTRACT OF ERGOT.
Ergot, recently ground and in No. 60 powder, 100; acetic acid (36 per cent.), 2; alcohol (49 per cent.), sufficient to produce 100. Average dose.—2 mils (30 minims).
Infusum Ergotae, B.P.—INFUSION OF ERGOT.
Ergot, freshly crushed, 5; distilled water, boiling, 100. Infuse the drug in the water for fifteen minutes, in a covered vessel, and strain. Infusion of ergot is an extremely active preparation of the drug when freshly made from well-dried ergot of good quality, but it is rarely used. Dose.—30 to 60 mils (1 to 2 fluid ounces).
Injectio Ergotae Hypodermica, B.P.—HYPODERMIC INJECTION OF ERGOT. Syn.—Hypodermic Injection of Ergotin.
Extract of ergot, 10; phenol, 0.3; distilled water, to 30. Six decimils (0.6 milliliters) contain 2 decigrams of extract of ergot (about 3 grains in 10 minims). Dose.—2 to 6 decimils (0.2 to 0.6 milliliters) (3 to 10 minims).
Mistura Ergotae, B.P.C.—ERGOT MIXTURE.
Each fluid ounce contains 30 minims of liquid extract of ergot, 10 minims of diluted sulphuric acid, and a sufficient quantity of chloroform water. Ergot mixture is used principally to arrest uterine haemorrhage and to promote uterine contraction. Dose.—15 to 30 mils (1/2 to 1 fluid ounce).
Mistura Ergotae Ammoniata, B.P.C.—AMMONIATED ERGOT MIXTURE.
Each fluid ounce contains 20 minims of liquid extract of ergot, 3 grains of ammonium carbonate, 15 minims of emulsion of chloroform, with a sufficient quantity of camphor water. Dose.—15 to 30 mils (1/2 to 1 fluid ounce).
Tinctura Ergotae, B.P., 1885.—TINCTURE OF ERGOT.
Ergot, in No. 20 powder, 25; alcohol (60 per cent.), sufficient to produce 100. Prepared by the percolation process. Tincture of ergot was formerly employed for the same purposes as Extractum Ergotae Liquidum. It has now fallen into disuse. Dose.—1/4 to 2 mils (5 to 30 minims).
Tinctura Ergotae Ammoniata, B.P.—AMMONIATED TINCTURE OF ERGOT.
Ergot, in No. 20 powder, 25; solution of ammonia, 10; alcohol (60 per cent.) sufficient to produce 100. Add the solution of ammonia to 90 of the alcohol, moisten the drug with 10 of the mixture, and percolate with the remainder; press the residue, mix the liquids, add sufficient alcohol to produce the required volume, and filter, after standing for twenty-four hours. Ammoniated tincture of ergot is used in a similar way to Extractum Ergotae Liquidum. Dose.—2 to 4 mils (1/2 to 1 fluid drachm).
Vinum Ergotae, B.P.C.—ERGOT WINE. 1 (liquid extract) in 5.
Used when a more palatable preparation than the liquid extract or tincture is required. Dose.—4 to 8 mils (1 to 2 fluid drachms).
Vinum Ergotae, U.S.P.—WINE OF ERGOT.
Fluidextract of ergot, 20; alcohol (95 per cent.), 5; white wine, 75. Average dose.—8 mils (2 fluid drachms).

The British Pharmaceutical Codex, 1911, was published by direction of the Council of the Pharmaceutical Society of Great Britain.

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