John Uri Lloyd, 1922: Alcohol Adversely Criticised.

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Alcohol in Pharmacy.

John Uri Lloyd, Ph. M., Cincinnati, Ohio. - Reprinted from The American Journal of Pharmacy, Aug 1922

"My Dear Mr. Editor:

"Perhaps I may best reply to the question you ask me regarding alcohol in pharmacy, by quoting from some of my old contributions to the Eclectic Medical Journal, which have not, so far as I know, drifted into pharmaceutical journalistic print. In some directions, as I read these over, revisions might be made, as is natural when one considers that the first was written forty-five years ago, but as a whole they might, in my opinion, stand as written.

"Believing that if you have the time to read these over they will practically cover the questions asked of me. I am

"Sincerely yours,

"(Signed) John Uri Lloyd."

Editor's Note (AJPharm 1922).—Nearly a half century has rolled by since Professor Lloyd penned the following contribution, but we frankly believe with the Professor that these old writings carry much that just at present is considered as "new thought" and also much that will give text for "advanced thought" to persons concerned in therapeutic pharmaceutical progress.

Alcohol Adversely Criticised.* **

* Part of an article in which the glucoside was the substance in hand, not the alcohol.
** From Eclectic Medical Journal, 1875.

Unless the pharmacist has made himself as nearly as possible conversant with the properties and chemical attributes of the substances that are naturally associated within the bark along with the glucoside, and is consequently enabled in preparing his pharmaceuticals to eliminate materials from his preparation that have proved themselves incompatible with the glucoside, we cannot say he has proved himself a master of his profession or made himself of much benefit to physicians in respect to this class of materials. Even though he may truly claim for his preparation that each minim represents completely the medicinal principles of one grain of the crude material, and that every fluid ounce contains the entire virtues of one troy ounce of the specified drug, still other than in the slight advantage which would arise from a mere change in form, his pharmaceutical is not superior to the crude drug.

However, some may take issue with me upon this point, and pointing as an example to the fluid extracts now so popular, say—"Are not the soluble principles of the drugs separated from the insoluble and inert materials which accompany them? Are not the insoluble and useless materials, such as lignin, cellulose, starch, etc., eliminated from fluid extracts?" And I will answer, yes. Here I can agree with you, for in this respect you have improved upon nature, but although you have separated these substances, you have added a foreign material that is, in overdoses, more to be disapproved of than the inert wood and starch, which at the utmost are merely objected to because they are worthless and tend by their presence to render the administration of the crude drug unhandy, perhaps a little slow in action in consequence of serving as an envelope to the medicinal principles of the drug, and thus preventing them from coming in contact immediately with the juices of the stomach.

But on the other hand, the substance you have replaced them by is a powerful medicine of itself. I knew physicians will generally agree with me, for although under certain circumstances it may not prove objectionable, in some cases it is decidedly to be disapproved of. I will warrant that every doctor who reads this article can recall to mind instances where he would have preferred that his patients should have taken two teaspoonfuls of starch rather than one teaspoonful of alcohol. But we shall come to this in its proper place.

(From Eclectic Medical Journal, 1889.)

I will admit in accepting the fact that alcoholic liquid representatives of plants are often desirable, we are being drawn in some directions over broken ground. In my opinion we should differentiate more; the rule of elaboration is usually a good one, but there are many exceptions to the employment of an alcoholic menstruum in plant extraction. The thrusting of a line of alcoholic fluid extracts (followers of the mediaeval alcoholic tinctures and essences) upon the profession has been conducive to injury as well as benefit.

Manufacturers and physicians together have broadly accepted in this direction without proper discrimination, and if my opinions are worthy of consideration, a halt should be called by physicians. . . . The introduction of a line of substances known as fluid extracts, made practically by a universal rule, has led, I believe, to some marked disturbances of this nature. Drugs that cannot properly be extracted with an alcoholic menstruum are often thrust forward as unquestionably represented in an alcoholic form.

Take, for example, the mucilaginous bark of the elm, a drug that should be stripped fresh from the tree, torn into shreds and suspended in cold water in order to produce the soothing, cooling mucilaginous drink that is so refreshing to feverish patients. Its richness depends on its freshness. Each day this infusion should be prepared anew, and the vessel containing it should be kept in a cold situation outside of the sickroom to avoid absorption of foul exhalations.

Is it not illogical to substitute for that mucilage a burning alcoholic "fluid extract" that neither can contain the mucilage of the bark nor replace to the parching patient the grateful drink that may be prepared from fresh elm?

Pass to the other drugs somewhat of this description, comfrey, benne, quince seed, chestnut, and the same rule may be applied. The fresh infusion made with cold water is the best preparation, and every drop of alcohol added is at the expense of the value of the preparation. I do not hesitate to say, in my opinion, a so-called fluid extract or tincture of such a drug is not a desirable preparation. . . . I rebel against such preparations as fluid extract of Kino and fluid extract of Catechu, and have displeased some patrons by refusing to make them. Other cases can be cited in which such inconsistencies occur, but it is unnecessary, although I might say that in my opinion a decoction of Apocynum is effective where an alcoholic preparation is useless, and that the elaborate formula of the United States Pharmacopoeia, 1880, produces a fluid extract of chestnut far inferior to an infusion of chestnut leaves. . . . I freely say that in my opinion this fluid extract hobby has been carried in some directions too far.

The apothecary, the manufacturer, the physician, seem to have crushed themselves together and regardless of compatibles or incompatibles, of consistency or of inconsistencies, have rushed headlong into an alcoholic craze. Deserving and commendable in many particulars, objectionable in others, I view fluid extracts as one of the stepping stones to a more perfect pharmacy, which, by a series of evolution, will produce (to be followed by) substances that will surely displace them in the future. They are a crudeness of the present, although they have improved our medicines in some directions by displacing others more crude, or given us more portable preparations. But they have in many instances crowded our shelves with preparations very much inferior to the decoctions and infusions, or even to the crude drugs, that have been displaced.

I do not propose to try to defend myself for the part I have taken in this record, for I do not deny that my zeal in the past has helped to fasten the habit on others, neither do I close my eyes to the fact that many manufacturing pharmacists and their friends may even now decline to accept the situation as I see it.

(From the Proceedings of the Ohio Pharmaceutical Association, 1889.)

The careful apothecary is often confronted with possibilities that the thoughtless may overlook and which an inexperienced druggist may never comprehend. I shall refer now more particularly to the changes that take place in preparations after they are made and while they remain in our hands; changes that may result in a continued variation of drug action from time to time. By reason of this variation the physiological force and therapeutic action of many medicines must surely with all physicians be more or less of an uncertainty.

We do not necessarily have to seek in out-of-the-way places for examples illustrative of the foregoing idea. Indeed, scarcely a day passes that the writer is not called upon to study the matter in one or more of its unrecorded, connected phases, and probably other persons are continually confronted with problems of a like nature.

There are various known causes for these changes in properties of pharmaceutical preparations, familiar examples being the action of light on mixtures containing some compounds of iron, especially phosphate, pyrophosphate and citrate; the slow disorganization of alkaloidal solutions (elixirs perhaps) of slight alkaline reaction; the decomposition and subsequent precipitation of acid solutions containing bismuth salts which often remain transparent for a considerable time and then suddenly fly to pieces, etc., etc.

These familiar examples may be named as preliminary to the consideration of others less known, among which I will mention the action of light on many organic solutions exposed thereto and the questionable power of alcohol in maintaining the medicinal force of some organic substances that are soluble in that menstruum. Passing the former (influences of light) I will in this paper confine myself to the latter, which many persons have, I believe, overlooked entirely. Indeed, I have never seen a reference thereto.

By way of a comparison, it may be stated that while it is true that alcohol has the power of suspending acetous fermentation when the alcohol is in large amount, it is no less true that in smaller amount it is an acceleration of such fermentation, being then a food of the ferment. Thus, vinegar of a quality that is unbearably sour, is practically made by gradually adding whiskey to weak cider, in which case the alcohol reverses its character and becomes a producer of acetic acid instead of a protector against acetification. Pass, however, that phase of the subject, which is well understood, and consider alcohol in quantities so great as to forbid the chance of acetic fermentation, and I am by no means convinced that in other directions it is the uniform preservative that some persons believe it to be. Upon the contrary, it has gradually dawned on my mind, from consideration of alcoholic solutions of many substances, that many bodies readily disintegrate in its presence.

True it is that albuminous substances are coagulated and cannot putrefy when immersed in alcohol, this illustration being typical of its preservative power in that direction and an example that probably prevents our questioning its power in others, by quieting suspicion. If the brain of a man be placed in a jar and covered with alcohol, it becomes hard, brittle, contracts by loss of water and is indefinitely preserved in its shrunken form; but even here I question if structural changes do not also occur to alter normal conditions. Water of structural life is not water alone. While the form structures of most anatomical specimens are preserved by alcohol by reason of its action on muscle and albumen, I question if their normal interstructural characters remain intact, even though putridity is prevented. Admit that the spirit has prevented putrefaction, has induced albuminous coagulation and acted as a common preservative in this instance in one prominent direction, the question remains unanswered as to its full power of preventing alteration of other substances in other directions.

In this field there may be an element of uncertainty where we have thoughtlessly passed without a question. Most organic bodies are susceptible of alterations that are not explainable as yet by recorded experiments. These changes take place either in the presence or absence of alcohol and may serve as visible illustrations of the subject under consideration, to a few of which I may properly direct your attention.

If certain (most) fresh herbs in a closed jar be impregnated with alcohol by pouring a small amount of alcohol into the jar filled with the herbs, and then agitating until the herbs are thoroughly saturated with the alcohol, it will be found that they lose their green color in a few hours, turning brown. The chlorophyl perishes rapidly in those parts of the plants above the surface of the alcohol, while those beneath its surface sometimes remain green a considerable time, imparting their chlorophyl to the alcohol.

Instead of preserving the chlorophyl in the parts of the plants above the liquid, the alcohol with which they are saturated hastens their decomposition, and a parallel experiment with a like jar of herbs without alcohol shows they will retain their green color long after the specimens saturated with alcohol have become brown or yellowish brown.

This experiment is easily performed and will illustrate the fact that under certain conditions plant constituents dissociate with increased rapidity in the presence of alcohol, which becomes then an accelerator of decomposition, and what is shown by the seen may perhaps indicate what occurs at the same time in other constituents of that plant structure with the unseen. It is more than likely that simultaneous dissociations take place in other plant constituents; indeed, from my present view there is no question on this point.

Make a tincture of the fresh green herb by covering it with alcohol, macerating it a short period and quickly filtering. The tincture will at first be of a rich green. Place it aside. Examination from time to time will show a gradual change to brown and at last the green color may disappear entirely, a red-brown liquid being the result. (1)

It may be argued by some persons that in this instance the destruction of chlorophyl is immaterial since chlorophyl is of no medicinal value. Accepting this view, we may, however, use the striking exhibition of alteration in color thus showing destruction of chlorophyl to permit us to question as to whether at the same time, as already stated, unseen dissociations may not be taking place in other directions. We thus may be induced to make comparisons of the results of continued investigations which formulated into a whole become of service.

Pass from fresh plants to those that are dry, for many persons, accepting the Pharmacopoeia as infallible, will refuse to accept as medicines other than those made from dry drugs. The precipitates that occur in tinctures and fluid extracts in the presence of an abundance of alcohol illustrate the fact that changes of some description are continually taking place in them. (2)

The sudden decomposition of fluid extract of Geranium maculatum, the complete disintegration of fluid extracts of Stillingia, Iris versicolor, Epigea repens and many others, whereby nearly all of the soluble solid constituents precipitate, indicate that alcohol fails to preserve these liquids from alteration. That these changes are partly of a chemical nature is indicated by the fact that astringency of the liquid then disappears, while the resultant magma is free from astringency with Geranium, Stillingia, Iris and others, and no part of entire material after decomposition is possessed of its former characteristic properties. Neither the serum that suspends it nor any other menstruum will re-dissolve this precipitate.

The gelatinization of tincture of Kino and Catechu are familiar to all persons and as we consider the subject in its familiar phases the lesson seems to be, interstructural alterations that ordinary amounts of alcohol fail to interrupt changing reactions often in constant process and that these alterations may even continue to the utter destruction of the natural association of the educts originally held by the alcoholic liquid.

We have so far considered only the alterations that visibly affect a plant solution and these have been cited as examples because they unmistakably illustrate what may take place in other directions in which the appearance of the liquid is not altered. Reasoning from the facts deduced from a study of the visibly known, it is probable that unseen changes fully as important may be occurring in other directions. Indeed, there is every reason to infer that rearrangements of integral constituents may be continually at work in many alcoholic liquids, the result often being the production of new soluble bodies. Owing to the fact that there are no chemical tests for the majority of fluid extracts, these conditions can only be determined by sensible methods. A fluid extract might become dismembered so far as its original organization is concerned, and this fact remain hidden from observation if the resultant products are of the same color and soluble in the same menstruum. Indeed, I am sure that many substances do thus disappear in the presence of even strong alcohol. Of course, the highly developed alkaloids are not likely to undergo much alteration, if any, but many very potent medicinal agents surely disappear entirely. Indian turnip covered with alcohol becomes insipid; (3) alcohol will not preserve its acrid tincture. Tincture of Rhus toxicodendron, intensely poisonous when first made, (4) gradually loses its virulence and at last is practically worthless. Tincture of Anemone pulsatilla loses its anemonin gradually and should never be carried over a season. Even a pure solution of anemonin in official alcohol disintegrates; it cannot be thus preserved. Other examples might be cited to show that energetic soluble principles of plants are not altogether protected from change by alcohol. After considerable attention in this direction I have accepted that we may well study alterations in alcoholic plant preparations with more than usual profit.

To sum up: In my opinion, any cause for uncertainty in the therapeutic power of a pharmaceutical preparation demands the attention and investigation of apothecaries and pharmacists. Alterations that occur in these preparations render the practice of medicine proportionately uncertain. Only by studious attention in the direction indicated in this paper can we hope to determine the extent of such alterations, and these studies with many preparations must be made before we can expect to correct the matter. In order to aid the physician, whose skill in diagnosing disease is valueless without uniformly active remedies to meet symptoms of disease expression, we must consider the foregoing subject in connection with others that also render remedies uncertain.

Finally, I must conclude that physicians have much with which to contend from variation of medicinal power of many of the fluids that are made from different qualities of drugs and by different applications of skill in working the same. In some important cases they also have to contend with liquids that are reliable when first made, but become worthless through age, regardless of the skill and care of the operator. In most cases these liquids are dispensed in full faith of their reliability, by reason of the confidence we have in the preservative power of alcohol.