This section is from the book "Materia Medica And Therapeutics - Vegetable Kingdom", by Charles D. F. Phillips. Also available from Amazon: Materia Medica And Therapeutics: Vegetable Kingdom.
Active Ingredients. - The corm and the seeds both contain a crystalline principle, which may be separated from a solution in dilute spirit in needles and prisms, and is called Colchicine, C17H19NO5. Pel-letier and Caventou believed it to be veratria in combination with gallic acid, but Geiger and Hesse proved this opinion to be erroneous. Colchicine is a powerful poison; the taste is bitter, but not so burning as that of veratria; it is destitute of odor, does not excite sneezing, and is soluble in water and in alcohol. With nitric acid it exhibits a play of colors commencing with violet. In the corm there are also contained fatty matter, yellow coloring matter, starch, gum, lignin, and a peculiar acid called cevadic acid. The active properties are partially taken up by water, readily so by alcohol, by dilute spirit, and by vinegar.
Physiological Action. - Colchicum is acrid and sedative, and to graminivorous animals generally poisonous. Hence they never eat the herbage unless it be inadvertently mingled with their fodder and unperceived by them, in which case it is apt to cause inflammation of the intestines and bloody evacuations, sometimes ending fatally. Storck, who, in 1763, published a pamphlet upon colchicum, administered it to dogs; the result being shown in vomiting, tremor of the limbs, and convulsive movements of the belly. The animals howled, passed urine in large quantity, had bloody evacuations and prolapsus of the rectum, and finally died. In some cases the dogs lay prostrate, languid and perfectly still, with feeble pulse, slow and often irregular respiration, refusing food, and having their eyes glazed and swollen. So peculiarly severe are the effects of colchicum upon dogs, that in France the medicine bears the name of mort au chien, and from my own experiments I can testify to its appropriateness. Cows, when they have eaten colchicum, lose all desire for food and water; they cease to ruminate; they suffer from running at the eyes and nostrils, and from a peculiar kind of diarrhoea; instead of diuresis, as in dogs, there is a tendency to diminution of the urine; the belly becomes distended, and the animal sinks into a half stupefied state.
Upon certain other creatures colchicum appears to produce but little effect. Experiments made with rabbits had scarcely any result beyond exciting some diuresis; upon frogs the effects were trifling and very temporary. In all observations made upon the action of colchicum, whether in regard to animals or to the human subject, it must be remembered that the drug varies in energy according to the period of the year at which the corms are collected.
In man, colchicum, administered in small and repeated doses, promotes the action of the secreting organs and quickens especially that of the intestinal mucous membrane. The skin, the liver, and the kidneys are affected by it much less obviously, and the nervous system, as a rule, seems quite as little apt to receive its influence. Headache and vertigo are stated to have sometimes occurred among the effects; and even results such as ensue from the use of narcotics have been ascribed to colchicum. But the symptoms in question, when manifested, were probably referable not so much to the action of the drug per se as indirectly to the exhaustion which follows the employment of excessive doses. For, if taken in excess, colchicum produces nausea, vomiting, colic in some degree, failure of appetite, coating of the tongue, borborygmi, and diarrhoea. Still larger doses intensify the emesis and bring on purging; the tormina and tenesmus become severe; and the stools resemble those of patients suffering from dysentery, indicating much intestinal inflammation. This last is a very special symptom of overdosing with colchicum. Finally, in doses beyond medicinal ones, eolchicum becomes, to man as well as to dogs, a powerful poison, death being ushered in by acute pains in the bowels, incessant vomiting, and renewed purging and tenesmus, accompanied by great prostration and clammy sweats.
The effects of colchicine have been tried upon a variety of animals. As with colchicum itself, the principal and most characteristic phenomena are those of its drastic operation on the alimentary canal; whether given by the mouth or applied to a wound, the alkaloid constantly produces these effects, while convulsions are a much more occasional result. Geiger destroyed kittens in twelve hours with doses of six-tenths grain, the symptoms being those of gastro-enteritis; and Bley found one-fourth, of this quantity fatal to a kitten of three months; vomiting, purging, and convulsions preceded death.
Various experimenters have obtained substantially similar results in operating upon rabbits, pigeons, and dogs. The researches of Schroff and of his pupil Heinrich showed that the fatality in animals was by no means constantly proportioned to the dose. Heinrich, however, himself took successively .156 and .312 grain of colchicine; the smaller dose, taken pure, caused an acrid and burning taste, nausea, retching, and an increased flow of saliva, lasting for several hours. The pulse was lowered about eleven beats during the first two hours. The larger dose, taken eight days later, produced similar symptoms during the first four hours, followed, however, by symptoms of severe gastro-enteritis, which did not disappear until the fifth day. Heinrich also describes a case of accidental poisoning, in which a girl, aged twenty, took less than one-fourteenth grain of colchicine; this caused pain in the stomach, repeated vomiting of green matter, liquid diarrhoea, drowsiness and collapse, with a pulse of ninety-six. There was also extreme dilatation of the pupils, with occasional convulsive twitchings of the right hand, and streaming perspiration of the face. The epigastrium was extremely tender, and there was bloody vomiting for eight or ten days. It appears that colchicine represents nearly, if not quite accurately, the total power of the fresh corm, and that it is eighty to one hundred times more active than the latter.
The general results of inquiries into the physiological action of col-chicum are probably summed up with accuracy in the words of Gubler: "Colchicum is a drastic purgative, accidentally an emetic, and indirectly a sedative of the circulation; a depressant diaphoretic, sialagogue, and a diuretic." The slowing effect on the pulse seems always to be produced where doses have been given just so large, or so often repeated, as to approach but not to reach the line at which decided gastro-enteritis sets in. The latter condition is attended by increased rapidity of the pulse.
Therapeutic Action. - At what date colchicum was first employed in medicine and for what diseases is not known, but its use reaches back at least to the sixteenth century. Storck, as above stated, published a pamphlet concerning it in 1763, which may be considered as the first attempt to obtain exact knowledge respecting its action.
As a specific for Gout, it was, however, that colchicum first obtained wide celebrity, and principally under the form of the Eau medi-cinale which became fashionable in France during the reign of Louis XV. The popularity of this preparation was immense at the time; in subsequent periods the reputation of colchicum has fluctuated, at times reaching an extraordinary height, at others sinking very low. This periodical discredit of the drug has perhaps been due to its varying strength, attributable to collection of the corms at improper seasons.
At present, and especially since the publication of Dr. Garrod's masterly treatise on gout, scarcely any one disputes the fact that, in the acute stages of the disease, colchicum has the power to produce a remarkable amendment of the symptoms.
Upon the inflammation and pain of acute gout it acts very directly, and Garrod observes that this action is independent of any evident purgation, sweating, or diuresis, though it is well known that large doses will produce those effects. Nevertheless there is no doubt that, in the treatment of many cases of gout, the increase of secretions is an important matter; and, instead of saying that colchicum is a specific remedy for gout, we may content ourselves with the assertion that it more powerfully affects the gouty than any other known form Of inflammation. It is also certain that colchicum is not a lasting and final remedy for gout; it does not prevent relapses, and its power becomes weaker on successive occasions, till at last it will not check pain and inflammation unless given in dangerously large doses. As regards what was at one time considered an unfailing action of colchicum, namely, an augmentation of the elimination of uric acid, Garrod has shown that this is at least very doubtful, and thus its claims for being regarded as a rational specific for gout are further weakened.
In Acute Rheumatism there are surprisingly different opinions as to the efficacy of colchicum. Dr. Garrod thinks that in this disease col-chicum does good, if at all, by controlling the heart's action. Many authorities describe it as not less remedial in rheumatism than in gout; Gubler speaks of it in the same terms for both diseases.
On the other hand, it is certainly the case that of late years colchicum has been losing its prestige in London hospital practice as a remedy for acute rheumatism, and is even considered by many physicians either useless or altogether noxious, as being apt to seriously embarrass the circulation.
It may, at any rate, be stated that the long-continued use of colchicum, or its employment in large doses, is not to be thought of in rheumatism. The peculiar anaemia which attends this disease produces an irritable weakness of the heart, which renders it liable to suffer alarmingly from the effects.
In certain Acute Inflammations we are often convinced by experience that colchicum exercises a happy influence, and yet it may be very difficult to say what is the modus operandi. In bronchitis, for example, we are often not at all sure whether the remarkably fortunate results of colchicum treatment are not really due to the fact that the chest affection is but a part of the gouty diathesis. The same remark applies to its use in ophthalmia.
In Fevers of a zymotic origin no one any longer thinks of recommending colchicum. It is far too treacherous a drug, looking to its power of suddenly depressing the circulation, to be worth resorting to on the chance of its producing some mitigation of the febrile symptoms.
In Nervous Affections, such as hysteria, chorea, etc., for which it was formerly recommended, colchicum is no longer considered of any value. To produce decided impressions on the nervous system we must give such doses as would always be more or less dangerous.
Among the miscellaneous uses for which it may be employed, colchicum is deservedly in favor as an addition to other aperients, when a slight increase of their activity is desirable. Half a grain to one grain of the acetic extract is thus often added to a small dose of colocynth or of aloes. Indeed, we may sometimes get a very effective combination by adding such a dose of colchicum to such a medicine as nux vomica, which otherwise might be quite unable to act as an aperient at all.
As a Diuretic colchicum can be no longer recommended. Its action is most uncertain, and, now that we possess such a diuretic as digitalis, there is no occasion to employ it.
Preparations and Dose. - Extr. Colchici Aceticum, gr. j. - ij. (.06 - .12); Extr. Colch. Radicis Fluid., m ij. - x. (.12 - .60); Vinum Colchici Radicis, m v. - xxx. (.30 - 2.); Extr. Colchici Seminis Fluid., mij. - x. (.12 - .60); Tinct. Colchici, mv. - xxx. (.30 - 2.); Vinum Colchici Seminis, mv. - xxx. (.30 - 2.).