[Article II]
Anasarcin and Anedemin
“Anasarcin” and “Anedemin” are the twin nostrums of cardiac pseudotherapy. They are dubbed “twin nostrums” not so much because of any similarity in their formulas, that being a minor consideration in the average nostrum, but because of the close similarity in their methods of exploitation, the therapeutic claims made for them, and the time and place of their birth.
It may be remembered that they both claim Winchester, Tenn., as their birthplace, and they appeared on the market at about the same time; furthermore, a comparison of the claims formerly made for both of them indicated that one mind conceived the main idea that lies back of their exploitation. While Anasarcin is especially dealt with in this article, much of the discussion applies with equal force to Anedemin.
A LUSH FIELD FOR NOSTRUMS
Cardiac disease, with its resultant renal involvement, is frequently encountered; and running, as it does, a chronic course, it offers an almost ideal field of exploitation for the typical nostrum vender. By a typical nostrum vender we mean one whose knowledge of his product is far below that of his appreciation of a certain element of human character. On this element rests the whole secret of the nostrum vender’s success. It is variously termed credulity, gullibility and childlike simplicity, but it is that which often causes even the most conscientious clinician to turn aside from the use of the best known and most dependable drugs at his command, in the face of disappointment and failure, and employ some vaunted mixture which, in his saner moments, he scorns to use.
Anedemin is said to consist of a “Scientific Combination of three of the more recently investigated members of the Digitalis Series, with Sambucus”; that is, of apocynum, strophanthus and squill with elder. It is difficult to know just what idea the statement that it is a “scientific combination” of these drugs is intended to convey, for it is unscientific to mix three drugs of this group for use in fixed proportion in a wide range of conditions, if indeed, there is ever any indication for their use.
The great disadvantages of strophanthus and apocynum pertain to the extreme uncertainty of their absorption from the gastro-intestinal tract. Strophanthus is occasionally absorbed promptly, sometimes so slowly that the therapeutic effects are not induced until an amount equal to several times that which would prove fatal if all of it were absorbed into the circulation has been administered, and, unfortunately, one cannot control the absorption which may continue until a fatal effect is induced. This is true to an even greater degree of apocynum, and it was due to the recognition of this fact that apocynum was not admitted to the U. S. Pharmacopeia IX, the committee on dosage having agreed that no safe and effective dose could be given.
THE COUNCIL’S PREVIOUS FINDINGS
In 1907 the Council on Pharmacy and Chemistry examined the literature used in the exploitation of Anasarcin and Anedemin and published its report. Anasarcin tablets, it was pointed out, were said to contain the active principles of Oxydendron arboreum (sour wood), Sambucus canadensis (elder) and Urginea scilla (squill), and the following claims were made for the nostrum:
“Does what dropsy medicaments have hitherto failed to accomplish.”
“Superior to digitalis, strophanthus, scoparius, squills, acetate of potash and the hydragogue cathartics all put together.”
“The only known relief and permanent cure of dropsies.”
“Unrivaled heart tonic.”
“The most powerful agent known.”
“Safe in administration.”
“Non-toxic as ordinarily administered.”
“Will nauseate some persons,” but “the reaction from the temporary depression is prompt.”
“In Bright’s disease, both the interstitial and parenchymatous forms of nephritis, acute or chronic, no remedy ... to equal it in efficacy.”
“Without increasing the debility of the patient or interfering with nutrition by producing loss of appetite ...”
“This treatment is to be continued without cessation until all symptoms of dropsy have disappeared.”
A comparison of the earlier claims with those now being made (see advertisement reproduced from the New York Medical Journal) illustrates one of the results of the work of the Council. Today the nostrum exploiter avoids the cruder forms of obvious misstatement, but continues to make, by inference, claims that are equally misleading. It will be observed in this case that a more cautious pen worded the later advertisement, but there is still evident the intent to convince the reader that Anasarcin is superior to the official drugs in the treatment of cardiovascular diseases. The facts are that Anasarcin is at best a dangerous remedy in the hands of the average clinician in the treatment of such conditions, and its use is at all times to be condemned.
No competent investigator has ever investigated the pharmacology of sour wood (Oxydendron arboreum), and it appears to have no therapeutic value other than that due to a slight acidulousness. Elder (Sambucus canadensis) contains a trace of a volatile oil as its most important constituent, according to the British Pharmaceutical Codex of 1911 (p. 908), but it is difficult to explain why a trace of volatile oil should be considered important. Elder may be dismissed without further consideration in connection with Anasarcin tablets.
THE PHARMACOLOGY OF SQUILL
This leaves only squill among the constituents of Anasarcin for consideration. Sollmann (Manual of Pharmacology, 1917, p. 409) in discussing the advantages claimed for squill over other drugs of the digitalis group, says: “Dixon, 1906, points out that any superiority is outweighed by its disadvantages: uncertain absorption; strong gastro-intestinal irritation.” Squill was formerly used as an expectorant and diuretic, the activity having been attributed to two amorphous glucosids, scillipicrin and scillitoxin, but Ewins, 1911, found these to be impure mixtures. A later investigator claimed to have isolated two glucosidal agents from squill, but similar claims have often been made only to be disproved later, and we know of no confirmation of the claims regarding the isolation of any pure principles from squill having any true typical digitalis action.
The statement quoted from Sollmann is accepted by practically all pharmacologists, and we may say with certainty that squill is decidedly inferior to digitalis in the treatment of cardiovascular, and cardiorenal diseases, and certainly no active principles of squill were known to the scientific world at a time that the remarkable claims were first made for Anasarcin by an obscure pharmacist of Winchester, Tenn. Indeed, if Anasarcin were all that it was claimed to be, its discovery would have made Winchester as famous as a certain Wisconsin city was said to have been made by a popular beverage.
It has been abundantly demonstrated, and it is now almost universally accepted among well informed pharmacologists and clinicians, that all digitalis principles exert the same kind of action on the heart after they enter the circulation in effective doses, though they differ to an extraordinary degree in the intensity of their action and in their undesired sideactions, such as nausea and vomiting. When the use of Anasarcin (squill) is followed by immediate improvement after digitalis has failed, it merely shows that the dosage of digitalis was insufficient or that it was discontinued and the squill mixture was substituted before the full therapeutic effects of the digitalis developed.
WHEN THE DIGITALIS GROUP IS CONTRAINDICATED
If the administration of a sufficient dose of digitalis is not followed by improvement in the circulation, it shows that the heart is incapable of responding to such treatment and the further use of any of the drugs of this group is distinctly contraindicated. This is confirmed by the experience of nearly every competent observer of digitalis therapy, and numerous fatalities have resulted from the failure to appreciate this fact and further administer some other member of the group, such as strophanthus or squill.
It is now well known that the cardiac effects of toxic doses of squill, and other members of the group, resemble closely those of cardiac disease, and it is often impossible to determine whether the behavior of the heart in a given case is attributable to insufficient dosage, to excessive dosage, or to the progress of the cardiac disease itself. If this occurs when one uses the best known members of the group, it is certain that it occurs even more frequently when others that are less understood are employed. In the light of this knowledge of the dangers attending the incautious use of any member of the digitalis group, and more especially the use of impure principles, such as are commonly obtained from squill, it is impossible to condemn sufficiently the recommendation that the use of Anasarcin should be continued without cessation until all symptoms of dropsy have disappeared.
Digitalis bodies are not suited for the treatment of all cardiac disturbances, and it is, of course, self-evident that a time must come in the treatment of chronic cardiac disease when the heart is incapable of responding to any form of treatment with improvement. But, unfortunately, it never loses its response to toxic doses, and to push the administration of any drug or mixture containing any drug of the entire digitalis group—and especially those, like squill, in which the side actions are most prominent—beyond the point of tolerance is to court certain disaster.
THE TREATMENT OF CARDIAC DROPSY
While it is quite certain that many lives have been sacrificed to the failure to understand this phase of cardiac therapy, it is equally certain that many lives have been sacrificed because of insufficient dosage, and one can steer a safe course between these dangers only by using the best known preparation available; and in the present state of our knowledge it is indisputable that digitalis and the tincture of digitalis are best suited for the treatment of cardiac disease except in those few cases in which intramuscular or intravenous administration must be employed temporarily for immediate effect.
The secret of prescribing successfully for the relief of dropsy in cardiac disease consists in understanding the effects of digitalis on the heart, in administering it until these effects indicate that the desired object has been obtained, and stopping, or interrupting, the administration at that point until the effects begin to wear off. Cumulation, so called, is a positive advantage in such cases. It merely means that the desired therapeutic effects once induced persist for a time, and that further medication is unnecessary during such persistence of action. Eggleston has recently shown (Arch. Int. Med. 16:1 [July] 1915; abstr., J. A. M. A. 44:459 [July 31] 1915) that the full therapeutic effects of digitalis can be induced in suitable cases within a few hours even with oral administration.
We are not aware of a single publication in which a careful, detailed clinical study of Anasarcin has been reported. The claims made for Anasarcin, past and present, indicate either a deliberate purpose to mislead or crass ignorance of the rudiments of pharmacology and therapeutics. The exploiters of the nostrum claim that thousands of physicians have found Anasarcin tablets of unsurpassed remedial value in the treatment of disorders of the circulatory system and of ascitic conditions.[244] It must be admitted that too many physicians have prescribed Anasarcin, otherwise the manufacturers would not have continued to spend thousands of dollars in advertising it in medical journals during a period of more than ten years.
Doctor, this article is meant to be a candid discussion with you, whether you use Anasarcin or not, because every clinician is vitally interested in the customs that obtain in the practice of medicine, and we wish to put a hypothetic question to you. Answer it, at least to yourself, in exactly the spirit in which it is put. Suppose that you prescribe Anasarcin for a patient who is critically ill with cardiac disease. He dies. Are you willing to tell the relatives frankly just what you used and the nature of the evidence on which you based your choice of this nostrum? Let the supposition be carried further and say that the case was hopeless, and agree that digitalis and all other drugs would have been equally ineffective. Granting all this, would your explanation satisfy? Would you in all candor dare to offer such an explanation? Try it as a hypothetic case before you are forced to apply it.—(From The Journal A. M. A., Dec. 8, 1917.)