For explanation of the action of arsenic on carcinomatous tissue it may be recalled that a cell poison such as arsenic first destroys the cells least capable of resistance, for example carcinoma cells. The external application of arsenical pastes indeed depends upon the elective relation of arsenic to carcinomatous cells.
Sancyoshi found that arsenic acted particularly upon young markedly proliferating cells. Others have referred to the production of fever by arsenic. Fever as a sign of cell protein destruction can have significance for the melting down of carcinomatous tissue.
The consideration of the metabolic process in the cells leads deeper. O.Warburg has shown that carcinoma cells show an increase of the anoxybiotic fermentative process at the cost of the oxidative. A depression of oxygen consumption in the cells is also known of arsenic. The assimilative action of the usual arsenical medication in the first phase can be explained by this. But if the anoxybiotic cell process gains a definite preponderance so the cell process gains a definite preponderance so the cell chemistry becomes carcinoma-like and finally goes over to anoxybiotic cell destruction. Thus arsenic can favour the transformation and the destruction of cell in the sense of carcinoma and it will depend upon the dose and the existing state of reaction of the organism whether such a stimulation through arsenic will result favorably.
Concerning the influence of bone growth by arsenic the observations indicate entirely the same as they did with phosphorus. The growing animal fed with arsenic has more strongly developed bones. The cortex is thick, under the epiphysis is a compact bone layer, the arsenic stratum, exactly like phosphorus. The Haversian canals of the compacta, are smaller, the spongiosa is transformed into compact bone, and foot bones are transformed into solid bones. Lardeli also saw rabbits with a thickening of the cortex from Valsinestra spring water.
Not much use has been made of the possibility of using arsenic as a stimulus for the bone building process, like phosphorus and the phosphates up to the present. Still the similarity of the two chemical neighbors is worthy of note in this respect.
THEORY OF ARSENIC ACTION
Up to the present we have found extensive analogy between the action of arsenic on the organ cells and capillaries with that of phosphorus. One might imagine that the cell poisoning effect of arsenic, as with phosphorus, is combined with the regular oxidative cell metabolism. The depression of oxygen utilization of the red blood cells favors this as well as the stimulating action on assimilative processes. The destruction of cells, the splitting of protein, and the necrosis then could be an anoxybiotic process. The capillary poison effect does not oppose this idea, moreover, the inflammatory action on the capillaries can be conceived as a prestige of fatty degeneration and of a necrotizing end-effect on the vascular endothelium. The hypothesis of Binz and H. Schulz, that the cell damage occurs through the oxidation of arsenious acid to arsenic acid and again reversely by reduction of arsenic acid to arsenious acid, also by a change from oxygen consumption to oxygen yield, does not seem generally applicable, particularly since the oxidation from arsenious acid to arsenious acid, has not been proven in the organism up to the present. From the very slow excretion of arsenic out of the organism one might plausibly conclude that arsenic enters into a very firm compound with cell constituents and by transformation of this constituent the cell function was markedly influenced, indeed the entire cell was finally destroyed.
The apparently promoting action of arsenic proves to be the result of depressing or destructive influences; the increased assimilation probably results from depression of oxidation, the increased bone building, indeed in analogy to phosphorus, is probably an over-reaction to bone destruction. A stimulating action on the blood is still not confirmed experimentally, consequently it is also not explained. From the clinical use however such an end effect is not to be doubted.
Experimental knowledge is still too rudimentary to provide a detailed explanation of the effect mechanism of arsenic.
ACTION ON SINGLE CELLS
Some data have been secured on the actions of arsenic on bacteria and protozoa. They have become particularly important because of the attempts to obtain a parasitotropic sterilsatio magna by the aid of organic arsenical compounds an atoxyl, salvarsan, etc.
If at first we study the bacterial action of inorganic arsenic, then it is striking that the arsenic sensitivity with single types of bacteria is entirely different. Streptococci, cholera vibrio and typhoid bacilli are injured by very small amounts of arsenic while staphylococci, coli bacilli and proteus not only retain life with great concentrations but even thrive. We also see closely related types of bacteria are influenced entirely differently. We need merely assume that also in the organism the defense against the toxins or the decomposition products is favored in the same way in order to understand that in homoeopathy arsenic has proven itself much more useful in streptococcus sepsis, cholera and typhoid than in the suppurations or inflammations provoked by staphylococci and coli. In homoeopathy arsenic is not employed in the infectious diseases named because these organisms are arsenic sensitive, but the guiding line is the similarity between the responses of the organism, on any side to the particular organism, on the other to arsenic. If now the germ which is able to provoke a “morbus arsenicalis,” that is, produces effects similar to those of arsenic, is sensitive to arsenic even in the test tube, then there exists a probability of a deeper connection: the chemical affinity of the arsenic to the germ under the complicated conditions of the organism might prepare them, as an opsonin does, for the assault of body, cells, and on the other side it would be exactly the skin cell powers with an affinity for arsenic which would be stimulated; arsenic also acts in consequence to its affinity on both sides as a link of the attack.
With the yeast and mold fungi similar conditions exist. Marked dilutions of arsenic (1:40,000) promote fermentative capacity of yeasts. Through small doses of sodium arsenite, not only fermentation but also the inversion property of yeast cells limited or removed and finally the yeasts are killed. Fungi are remarkably insensitive to arsenic and single forms have the capacity to convert solid arsenic compounds into gaseous forms, as is recognized by the garlic-like odor. These types also seem to be affected in respect to the vital activities precisely by large amounts of arsenic.
The effect of reciprocal play between arsenic and the cell is also not dependent simply upon the elected dose, but essentially upon the peculiarity of the cells. Naturally we have as yet no view regarding the chemical basis of these differences. Perhaps the phosphate content of the cell has significance.
Especially important for chemotherapy is the action of arsenic on protozoa. Here rapid killing is found with great doses, with moderate doses growth but death after a longer time, in markedly dilute solutions (1:10-20 million), on the contrary, increased growth. We will do well not to consider according to a simple schema; stimulation, depression, death but the reciprocal play between living organisms and poison should be considered as a struggle under definite conditions, in which now the living organism and now the poison is victorious. The stimulating stimuli can be understood as an over-reaction to a damage, just as perhaps the excessive new formation of bone in arsenic poisoning; one cannot as yet say that this is a stimulation, an increase of vital activity. For example it can be doubted whether the cells stimulated through the smallest doses of arsenic have the same duration of life and functional capacity as would occur under the usual conditions of life.
Likewise among the protozoa it seems that single types are especially sensitive to arsenic and indeed the trypanosome. Naturally in experiments with arsenic that one does not kill the trypanosome intra corpus, but they diminish in the blood only transiently.
An improvement of parasitotropic actions has been sought as is well known by means of the organic compounds of arsenic. Arsenic is contained in these in a non-dissociating form which reduces the toxicity for body cells. At least it takes longer in the cells to liberate arsenic from an organic compound than an inorganic or dissociable form. Moreover, it is assumed that the distribution of such organic arsenic compounds in the various cells is different than with the inorganic and that they can reach other cells before they are split so that an enrichment is obtained which would not be possible with an inorganic arsenic compound because the latter would produce an acute action on the body cells. The question is simply, how far the union to the parasites (spirochetae, recurrent spirilla, trypanosomes) is obtained a still undecided question.
The cacodylate (a secondary aliphatic arsenic compound) has indeed quantitatively less toxic action than inorganic arsenic, but qualitatively the same and seems otherwise to possess no therapeutic advantage. Atoxyl (that is, the sodium salt of pamino-phenylarsinic acid, also a benzol compound) has proven effective against trypanosomes and certain spirilla diseases although it has no action on these organisms in vitro. A participation of the organism (perhaps a conversion into another compound) must occur. The alterations in the direction of effect express themselves in a stronger injury to the central nervous system, in particular of the optic nerve and retina (blindness), ataxia, loss of reflexes, furthermore, in the previously mentioned degenerative blood picture (poikilo-and anisocytosis). The related arsacetin (acetyl-p- aminophenylarsenic acid) is supposed to be less toxic, but more effective in trypanosomiasis and recurrens. Spirocid or stovarsol (acetyl ester of p-oxy-m-aminophenylarsinic acid) is supposed to have the advantage of a good spirocheticidal action by oral administration, but is extolled particularly for injection in Plaut-Vincent angina. Finally most used is salvarsan (besides its compounds, neosalvarsan and silver salvarsan and neosilver salvarsan). Ehrlich obtained these products by the reduction of phenylarsinic acid because he assumed only from such a reduction of phenylarsinic acid compounds in the body a parasitotropic action is obtained. Salvarsan is the dichlorohydrate of dioxy-diamino-arsenobenzol.
Spirochetes and trypanosomes can surely be diminished in the blood by salvarsan, but for how long, is another question. Moreover increased salvarsan fastness of the parasites must be considered, therefore treatment in the early stage has rich prospects. On the therapeutic results and the possible injuries from salvarsan I cannot enter here; I can, however, from personal experience contradict the report that no blindness occurs in salvarsan in contrast to atoxyl. The social hygienic value of salvarsan therapy in syphilis however ought not be questioned.
Malaria, recurrens, lues, particularly in the primary stage with phagedenic ulcers represent a field of employment for arsenic also in homoeopathy. The meaning of organic compounds perhaps may be conceived in the different combinations of arsenic effects by the organism. And “another binding”, however, is probably associated with an alteration in the amount, the concentration and the frequency of doses and thus permits the great diversity of possibilities of influence with arsenic to be understood.
The uses still in vogue in the school today are blood diseases, states of weakness with emaciation and skin disease representing merely a limited and insufficiently definite section out of the great domain of action of this polycrest. The doses of water cures (5th-6th potencies) do not differ considerably from those in homoeopathy.
The paths and type of actions of arsenic in the human organism are known through thousands of poisonings even if the effect mechanism is dark in single details. The provings of the healthy with various potencies have only the meaning of improvement and refinement of the symptomatic picture; first for improvement of the early symptoms, which especially arise in the vegetative, regulatory, vasomotor-trophic disturbances, the modalities, among which the well known symptoms of arsenic appear from the poisoning.
Intentional provings of arsenicum album are found:
1. Hahnemann: Materia Medica Pura, 3 Aufl. Bd. 2, p 41, 1833, and Chron. Krankheiten, 2 Aufl. Bd.5, 1839.
2. Imbert-Gourbeyre: L’Art Medorrhinum, Bd. 17 p.433.
3. Robinson: Brit. Journ of Hom. Bd. 25, p. 320.
Of Natrium arsenicosum:
1. Trans. of Penns. State Hom. Soc. II, 186 (according to Allen’s Encyclopedia, vol. 6, p.473).
2. Imbert-Goubeyre: L’ Art Medorrhinum Bd. 17, p 440.
Of Arsenicum iodatum:
1. Beebe: U.S. Medorrhinum and Surg. J. vol. 1, p.339.
2. Blakeley: Hahne. Monthly, vol. 3, p. 265.
3. Thomson: Lancet, 1838/39, p 176 (Allen Encyclopedia, Bd.1).
4. Hale: New Remedies, 4, Ed., p 372 1875.
Of Cuprum arsenicosum:
Hale: New Remedies, 4 Aufl. p. 74, 1875.
STEP-LIKE GRADES OF ACTIONS
In the domain of arsenic action various steps can be differentiated. The most crude local necrotising action of the cell poison corresponds to the malignant septicogangrenous and embolic processes, phagedenic ulcers with offensive, often cadaverous, acrid secretions, ulcers which bleed easily and possess the general characteristic of the remedy, the burning pain. At another step stands the blood destructive action resembling a pernicious anemia and the general cachexia. A further section is designated by the capillary poison effect which stands very close to phosphorus. It is from the poisonings which run acute and subacute courses that all the acute inflammatory manifestations on the mucous membranes and parenchymatous organs with the final result in fatty degeneration are embraced. The organic heart and vessel damage represents the severe cardiovascular syndrome at this step. The neuritic and trophic disturbances correspond to a more chronic course. Finally there are the vegetative and vasomotor symptoms and allergic states which characterize a grade of special arsenic sensitivity and which appears only at times in the beginning of chronic action or in a sufficiently fine intentional proving. The accompanying psychic symptoms can in any case show all stages of the most profound melancholia, greatest unrest and anxiety of the acute intoxication and excessive sensitivity.
In the most severe general diseases, malignant tumors with cachexia and pernicious anemia, arsenic belongs to the similar but still only rarely helpful remedies. From antiquity ever again one returns to arsenic, obviously, because occasionally good was obtained from it in such dubious cases. In spite of improvement of the knowledge of indications the homoeopathic method has often employed it in these destructive processes but the situation is so dubious that convincing results are rare. In malignant lymphoma arsenic is likewise generally used. One may see a temporary result from arsenicum iodatum D 3.
In the severity of cell action, the firmness of combination, the generality of effect possibility and the preference for the parenchymatous cells, arsenic can be best compared with the most virulent toxins of many bacteria; therefore the great similarity of the arsenic picture with cholera, with acute sepsis as well as those with a more protracted course.
The similarity to sepsis can serve at first for enlightenment of certain general actions of arsenic.
COMPARISON WITH SEPSIS
In sepsis as in arsenic we see the high grade weakness, so difficult to explain by tissue sections, increasing anemia from diminution of the erythrocytes and of the hemoglobin. The anemia, in arsenic has an entirely toxic degenerative note and between the degenerative anemia and the fatty degeneration of the organ and endothelial cells certainly exists some connection because the fatty degeneration is observed especially in pernicious anemia. The extreme anxiety and restlessness in addition to the great weakness, and the feeling that death is inescapable, one finds in arsenic in sepsis. The chills in sepsis correspond to the periodic chills and the so-called cold fever in arsenic. The periodicity cited as so characteristic for arsenic is not strict but depends upon the periodicity of metabolism. It expresses itself in a chief time of aggravation namely from midnight to two in the morning. The great feeling of coldness, the desire for warmth the improvement from warm drinks, corresponds to the collapse phase of sepsis (and cholera) and is also more peculiar to the acute arsenic picture while the mild vasomotor phenomena, as headache, improvement from cold have and what suggests the congestive nature of these aggravation from lying down. The cold sensation of arsenic apparently has less constitutional character than an acute, and this modality is not universal, but merely, similarly to phosphorus, is present in a reversal to some other condition. The great thirst of the arsenic picture is characterized by frequent ingestion of only small amounts of fluid. This corresponds to the great restlessness in which, just as in sepsis, the organism is found in an acute arsenic status. In the more chronic states, absence of the thirst is not a contraindication to arsenic.
The similarity of arsenic and sepsis can be followed further in respect to the manifestations in single organs. If one recalls the malignant, septico-gangrenous anginas and oral inflammations, the parenchymatous nephritis, as they occur in sepsis and scarlet fever just as they do in arsenic, then one frequently finds a suitable remedy for them in arsenic; in the toxic but still therapeutic cardiac action, myocarditis, dilation with arrhythmia, bad pulse, lowering of the blood pressure and coldness of the body, as well as endocarditis; in the splenic swelling, in the erythematous and at times petechial skin phenomena, all of which refer to the septic character and to arsenic as a suitable remedy. A toxic herpes zoster with the characteristic burning pain also falls in the field of indications of arsenic and also appears in sepsis. To these are added the septic and phagedenic ulcers of arsenic on the skin and mucous membranes which tend to become gangrenous, likewise with burning pain, the corneal ulcer. Ulcera cruris has more a trophoneurotic character; its black base, the flat extension in width, indicates the poor tendency to healing. Thrombophlebitis and septic-embolic foci suggest arsenic as one of the most important remedies.
Such a comparative consideration shows that arsenic has been an important remedy in sepsis in homoeopathy but is in no way always the remedy. Here the character and rhythm of many arsenic symptoms should be distinctly comparable. It is worthy of note that (according to Gies) arsenic is considered an antidote to snake bite among the Brahmins.
COMPARISON WITH CHOLERA
The comparison of the most severe gastro-enteritis of acute arsenic poisoning to the picture of cholera is likely. Even Virchow could not differentiate between arsenic poisoning and cholera from the pathologico-anatomic findings. The signs of arsenic are: rice water stools, great lassitude, severe colic, cardio-vascular collapse, cramps in the calves, ice cold body, fear of death, aggravation of the diarrhoea and of the vomiting from eating and drinking as well as at night, with burning thirst, aggravation from cold drinks which are vomited immediately, improvement from warm drinks and the application of other forms of heat. If convulsive phenomena appear, then cuprum arsenicosum will be preferred. The comparison is naturally drawn only to the picture and not to the diagnosis. In cholera infantum arsenic or an arsenical compound is frequently in place, but it can, for example, be just as well indicated in the similar botulism or paratyphodial diseases, also in gastro- enteric conditions with less severe total pictures which are provoked by cold foods or drinks or spoiled foods. The diarrhoeas are always extremely offensive, at times bloody, very exhausting, so that a dysentery-like picture comes into consideration for arsenic. The abdomen is sensitive to pressure and distended. Throughout the entire gastro-intestinal canal a severe burning pain prevails, thus, for example, in the markedly inflamed hemorrhoids in which the nocturnal aggravation and the improvement from warm applications furthermore suggest arsenic. Cold foods and drinks cause gastric pain, vomiting, and diarrhoea. The great weakness and the other modalities are always guiding.
OTHER MUCOUS MEMBRANE SYMPTOMS
The gastro-intestinal canal syndrome in arsenic need not manifest septic and toxic trend which corresponds to cellular and capillary damage. Thus arsenic can be helpful in gastric ulcer with burning pain where in all probability vasomotor-trophic causes rather than toxic causes play the chief role. The following gastrics symptoms of arsenic can have gastritis as a basis: pain after eating and drinking, sour burning and eructations of sour and bitter but very acrid fluid, loss of appetite, great aversion to food, can hardly bear the sight or odor of foods, longing for acid and coffee.
On other mucous membranes and organs the transition from organically inflamed to vasomotor disturbances in arsenic is still more distinct. Thus in the respiratory organs there is less often septic lung inflammation or pulmonary gangrene; likewise catarrhs of the respiratory passage (with dry cough, pain in the chest, aggravation after midnight, from drinking and in cold air) are rarely arsenic indications; more frequent are the asthmatic states with the typical time of aggravation, anxiety and restlessness and the inability to remain recumbent, accompanied by a dry hacking cough and a sensation of oppression and a scanty foamy expectoration. Hahnemann cured himself of a threatening suffocative catarrh which was aggravated each night after lying down by the use of arsenic. It is also not excluded that a chronic bronchitis with emphysema lies at the basis of the asthma. Moreover the nervous allergic forms of asthma react very well to arsenic which then is naturally given in the higher potencies. For explanation one can refer to the heightened irritant state of the respiratory center in arsenic poisoning; moreover the early action on the capillaries which is associated an abnormal permeability can also be made responsible. Finally the eosinophilia and the leucopenia under arsenic are signs of a simultaneous action on the autonomic system.
On the nose an actual inflammation with thin watery, acrid secretion is present with burning and sneezing without relief; but also the allergically precipitated hay fever or the vasomotor rhinorrhoea is a good indication for arsenic. In any case the aggravation in the open air holds more for the latter form.