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Article I.—Notes and Observations in Medical Practice. By Robert Christisox, M.D., V.P.R.S.E., Professor of Materia Medica in the University of Edinburgh. 1. On Digitaline. 2. On Preserved Meat-Juice.
1. On Digitaline.
So far as I am aware, no mention has yet been made in English works of any observations made in this country on the properties and uses of Digitaline, the active principle of foxglove. Nevertheless few substances would seem to deserve more attention. Digitalis is the best diuretic which medicine yet possesses; as every one will admit who studies its actions and the conditions for developing them. It is also thought by some to be one of the best sedatives of the circulation yet known; which, however, appears to be by no means so well ascertained. At the same time, all who use it have found reason to lament the uncertainty of its effects; a complaint, which, though sometimes unjust, because arising from insufficient acquaintance with the conditions for success, is clearly also often well founded, and dependent on the irregular strength of the galenical preparations of the plant, and the impossibility of trying their quality by any sensible properties or chemical test.
It is long since medical chemists were led by the great importance of foxglove to attempt to relieve medical practice from one source of uncertainty by endeavouring to discover its active proximate principle. At first these attempts were but partially successful. Its properties were concentrated at last in a pitchy extract of intense energy. But the very energy of this extract was only an additional objection to a drug whose form could not ensure uniformity of
IfEW SERIES.—SO. I. JANUARY 1855. A
strength, and left the really active principle in a condition liable to decay. The cause of difficulty in analysing foxglove was at length found to depend on the extreme instability of its active constituent under chemical operations. But after many years of fruitless search, MM. Homolle and Quevenne of Paris finally succeeded in detaching it in the form of a permanent, white, pulverulent Digitaliue of neutral chemical relations.
Soon afterwards the same gentlemen proceeded to institute a searching inquiry into the actions of their newly discovered body. Their observations, as well as those of other French physicians, have been published from time to time in the useful little Annuaire de Therapeutique of M. Bouchardat; and in January last their final results have been given in an excellent detailed treatise entitled, Mkmoire sur la Digitaline et la Digitate. The researches of MM. Homolle and Quevenne clearly establish, what every scientific cultivator of therapeutics must long ago have confidently anticipated, from the analogy of other active plants which had been successfully analysed,—that the poisonous and medicinal properties of foxglove reside entirely in a peculiar proximate principle. Considering the apparent disconnection of the two leading and widely-different properties of the plant, its diuretic action on the kidneys, and its sedative influence on the heart, it might very possibly have been found to contain two active constituents, one for each property; and such sub-division would have proved a veiy convenient and desirable discovery for medical practice. Unhappily, as hitherto appears, both actions are concentrated in one principle, though the plant has been found to yield several others.
About two years ago, having obtained favourable results from a trial with Digitaline of French manufacture—for at that time I could not learn that any was prepared in Britain—I requested Mr Morton of London to prepare some for an extended trial of its effects. This gentleman, with his accustomed accuracy, supplied me with two forms, as suggested and employed by MM. Homolle and Quevenne,—a brown extractiform substance and a pale greyishwhite powder. When the remedy comes into general use it is to be hoped that the latter form will alone be sanctioned. But, in the meantime, no harm can come from using the less pure form when supplied from a known and trustworthy source, and given strictly according to the injunctions of the discoverers. I therefore have hitherto used the extractiform digitaline alone, but the same sample ofit.
My experience of its effects has been highly satisfactory. I have used it expressly as a diuretic only; but its sedative virtues have also come incidentally under observation; and it is quite evident that digitaliue is a most energetic remedy in both ways.
In the first two trials made with it, which were both of them in cases of extensive, protracted, obstinate oedema in connection with disease of the kidneys, diuresis commenced, in one towards the close of the second day, and in the other a day later; in both the flow of urine was profuse; and in both the oedema entirely disappeared, but with the slowness not uncommonly observed in this form of dropsy.
Here I cannot help observing in passing, that a striking illustration was presented, on both these occasions, of the unsoundness of the objection which has been brought by many practitioners, since it was first propounded by Dr Osborne, against the use of diuretics in the renal forms of dropsy. I have taken every opportunity, in my clinical lectures, and in occasional publications, to protest equally against the unsoundness of the theory and the looseness of the facts, which have led to the prohibition of diuretics in renal dropsy, and which have deprived many persons of the most immediate and most efficacious means of relief from the principal secondary affection occurring in Bright's disease of the kidneys. And I may here repeat, in the strongest terms, that I have never, except in a single instance, seen the albuminosity of the urine, or any other indications,—which either the other conditions of the urine or any other local symptoms can furnish,—increased under the employment of such diuretics as I have given in this disease. These are digitalis, squill, and bitartrate of potash, sometimes singly, more commonly combined. What may be the case with other diuretics, I shall not pretend to decide. I strongly suspect that they are all in the same category, and that they have been shunned on grounds purely theoretical and baseless. But at any rate I can answer for the theory not holding in the case of the three diuretics I have mentioned. So, too, in the case of digitaline. It is not a little remarkable that in the first two patients to whom I administered it, the albumen, instead of being increased, was quickly and greatly diminished. In one it disappeared entirely in a few days, and did not return so long as the patient remained under observation in convalescence. In the other it also disappeared; but after some days the albumen reappeared, though in a greatly diminished proportion. Digitaline, therefore, while it stimulates the kidneys to increased secretion, has not, in so doing, any effect, as some have thought of digitalis and diuretics at large, in increasing the peculiar renal irritation which constitutes or occasions Bright's disease.
Digitaline has proved equally, or even more serviceable in dropsy connected with disease of the heart. It has, in my hands, accomplished complete discharge of the dropsical effusions, and thus effected such relief as to enable the patient to return to his occupations, though given in circumstances apparently very desperate. In this respect digitaline has done no more than is often accomplished by foxglove itself. But it has appeared to me to act with more speed, and with greater force after the action did begin. In one instance great depression of the heart's action was brought on instead of a flow of urine.
I have also given it in some local dropsies, more especially ascites, either simple or combined with anasarca of the lower part of the body only. It has not proved more useful, however, as a diuretic in these cases than digitalis and other diuretics; which in general fail to influence the urine or remove the dropsical effusion, when given internally. I have not yet tried it externally, according to the method recommended by me with infusion of foxglove.1
There can be no doubt that digitaline possesses the action of foxglove itself upon the heart and circulation. I have not made express trial of this action. But while using it to excite diuresis in a case of dropsy with diseased heart, the pulse began to flag, soon fell to 44, and became very soft and somewhat irregular. At the same time languor, nausea in a slight degree, and faintness ensued. All these symptoms disappeared in a few days after the remedy was discontinued. On this occasion I observed that the two actions of digitaline, its diuretic and sedative actions, do not concur. It is very likely that they are even incompatible. This I have formerly stated to be a probable fact in regard to the actions of foxglove.2 The disregard of it is, I apprehend, the reason why some underrate the efficacy of foxglove as a diuretic. Attention should therefore be paid to the fact in using digitaline.
The dose to be administered is stated by MM. Homolle and Quevenne at a seventy-fifth part of a grain of digitaline, three times a day. I have never given any other dose. It is a very small one certainly. But a tenth of a grain will kill a little dog; so that the dose is only in proportion to its exceeding energy. The form I have used is that of a pill about a grain in weight. It is to be given with the conditions and precautions observed in using foxglove.
Digitaline may be extracted from any part of the Digitalis purpurea; and it has also been obtained from the D. lutea. The leaves of the former yield as much as any other part of the plant, even as the seeds, and more conveniently. The dry powder is first saturated with cold water by the process of displacement. The di-acetate of lead is then added, to throw down much inert matter. The excess of lead is removed by a mixture of carbonate and phosphate of soda. Lime is next thrown down by oxalate of ammonia. Digitaline in an impure state is now precipitated by tannin, collected, and dried with a gentle heat, after being mixed with litharge, to detach the tannin. The dry powder is then made to yield a dry alcoholic extract by means of alcohol of the density of 836. From this extract, impurities are washed away with a little higldy-concentrated sulphuric ether. Digitaline alone remains.
The process is troublesome, but will probably be simplified. The product is consequently expensive. But after all a cure with it is not costly, by reason of its extreme energy. It is of good quality, if a solution in 200 parts of alcohol do not lose its bitterness until
1 Edin. Monthly Journal of Med. Science, 1850, xi. p. 310.
so diluted with water that the digitaline forms only a 200,000th of the solution.
Digitaline of this degree of purity constitutes pale yellowish-white scales, easily pulverizable, intensely bitter, intensely irritating to the nostrils, and permanent in the air. It fuses about 212°, and undergoes decomposition at a temperature somewhat higher. It is neutral, and destitute of azote; soluble in 2000 parts of water, and in 100 parts of pure sulphuric ether; very soluble in alcohol, and still more so in chloroform. It cannot be crystallised or combined with acids. Strong hydrochloric acid forms with it a beautiful grass-green solution. Potash added to its watery solution destroys its bitterness and substitutes astringency. The alkaline carbonates and caustic ammonia have the same effect, but act more feebly. Tannin throws it down from its solution in water.
Foxglove yields by analysis three other neutral proximate principles, which MM. Homolle and Quevenne have called digitalose, digitalin, and digitalide; but it may be surmised that these are the results of chemical reactions, and not true educts. There seem to be also three vegetable acids, called digitalic, antirrhinic, and digitolelc acids.
Bouchardat and Sandras found that the seventh of a grain of digitaline, injected into the jugular vein of a dog, soon caused frequent vomiting, staggering, diminution of the pulse from 120 to 36, giddiness, and death in four hours and a half. A grain and a half caused death in 90 seconds. Three-fourths of a grain secured in the stomach caused violent eltbrts to vomit, extreme exhaustion, and death in three hours. In the dose of a twelfth of a grain they found that in man it occasions reduction of the pulse to one-half or twothirds of its natural frequency, with disturbance of the senses, confusion, and fatiguing dreams, but only in one instance an increased flow of urine. Stannius ascertained that, in animals killed by digitaline, the heart, immediately after death, is motionless, and not excitable by galvanism, or any mechanical stimulus; while the voluntary muscles and intestinal muscles continue irritable as usual.
MM. Homolle and Quevenne have given in their treatise many cases of their own and of others, on the internal action and uses of digitaline. The general result is, that, in the dose of a 75th of a grain, given three times a day, it usually acts as a diuretic in general dropsies, and with great speed and efficacy in reducing the effusion; that this action on the kidneys is not so certain where there is no dropsical effusion, but nevertheless may be often brought on in other circumstances also; and that it is not rendered more certain by any material increase of the dose. The next result is, that in about double the dose, and sometimes in the same dose, it reduces greatly the frequency of the heart's action, arresting at the same time irregular action of functional origin, and even sometimes that connected with organic disease of the heart, and relieving palpitation. Lastly, the dose cannot reach the twelfth of a grain without