Arsenicum

Arsenic

Acidum arsenosum; arsenous acid. Acide arsénieux, Fr.; Arsenige Saure, Ger. Dose, 1/30 - 1/10 grain.

Arseni Iodidum

Arsenic iodide. Is an orange-red, crystalline solid, soluble in 7 parts of water, and wholly volatilized by heat. Dose, gr. 1/20.

Liquor Acidi Arsenosi

Solution of arsenous acid. Dose, τη ij —v.

Liquor Arseni et Hydrargyri Iodidi

Solution of arsenic and mercury iodide; Donovan's solution. Dose, τη ij—v.

Liquor Potassii Arsenitis

Solution of potassium arsenite. Fowler's solution. (Arsenous acid, potassic bicarbonate, compound spirit of lavender, and distilled water.) Dose, τη ij—x.

Liquor Sodii Arsenatis

Solution of sodium arsenate; Pearson's solution. Dose, τη ij—xx.

The organic compound of arsenic called cacodylic acid has recently come into use. It is much less poisonous, and its combination with sodium is freely soluble in water and can be given subcutaneously

It is used successfully in the treatment of pernicious anaemia and in incipient phthisis. The dose of this salt is from one grain.

When a course of arsenic is begun, large doses should be prescribed, and the quantity administered should be regularly reduced. In this way chronic arsenical poisoning is avoided. When continually increasing doses are given, the arsenic accumulates, and toxic symptoms are quickly induced. As a rule, unless very small doses are prescribed, arsenic should be taken after meals. Some subjects are soon seriously affected by even small doses of arsenic. For this reason, when the idiosyncrasies of the patient are unknown, it were better to make tentative experiments with a few small doses before beginning with large ones. A few drops of laudanum given with arsenic will enable it to be better borne by some susceptible subjects.

Antagonists and Incompatibles

The salts of iron, magnesia, and lime, and astringents, are chemically incompatible. The arseniate of iron, although not actively so, does cause toxic symptoms if continued in full medicinal doses. The hydrated sesquioxide of iron, freshly precipitated, and in a soft magma, is the antidote to arsenic in, solution. About eight grains of the antidote are required for each grain of the poison swallowed. As the hydrated sesquioxide of iron is harmless, it should be given in teaspoonful to tablespoonful doses, every few minutes. In every case of poisoning by arsenic, prompt efforts to secure evacuation of the contents of the stomach are necessary. Large doses of the antidote may be given with the emetic employed. In the absence of the hydrated sesquioxide of iron, magnesia, chalk, and lime-water may be given freely. These agents act in part, and probably chiefly, mechanically, by enveloping the particles of arsenic, and so hindering absorption. It is held by some that freshly precipitated hydrate of magnesia is more effective as an antidote than the hydrated sesquioxide of iron. Large draughts of oil, milk, and substances containing mucilage, by protecting the mucous membrane, render important service in cases of arsenical poisoning. Dialyzed iron, later experiences show, is quite as efficient as the hydrated sesquioxide, and is always ready. It is an important point to favor rapid elimination of the poison when the patient survives the acute symptoms. This is accomplished by the use of diluent drinks, skimmed milk, slightly alkaline mineral waters, etc.

Synergists

All those agents which promote constructive metamorphosis are synergistic to arsenic.

Physiological Actions

Applied to the tissues, arsenic excites violent inflammation and causes destruction of the part; it is therefore, an escharotic. Great pain attends its action. In consequence of the high degree of inflammation which it excites, when applied in sufficient strength, absorption does not follow its local use, but weak applications may excite dangerous symptoms by diffusion into the blood.

Symptoms of poisoning follow the inhalation of arsenical fumes, Numerous instances have occurred in which wall-papers colored with arsenical pigments have poisoned the occupants of an apartment. Garments covered with aniline dyes, fixed by arsenical mordants, have induced local ulcerations and systemic symptoms from absorption of arsenic. Applications to a large portion of even the unbroken integument, and to ulcerated surfaces, have, in numerous instances, excited dangerous symptoms, and have produced fatal results. That arsenic, wherever applied, manifests a selective action on the mucous membrane of the respiratory and digestive tracts, is a curious fact.

Arsenic, in small medicinal doses, promotes the appetite and digestive functions, and improves the body nutrition. It increases secretion of the gastro-intestinal mucous membrane, and hastens the peristaltic movements. Arsenic diffuses into the blood with facility. It probably enters into combination with the red blood-globules. It certainly lessens the excretion of carbonic acid, probably also of urea; in other words, it checks the retrograde metamorphosis. It stimulates the cerebral functions and induces a feeling of well-being, and in some subjects decided mental exhilaration.

In larger doses, yet not in quantity to produce acute poisoning, and when full medicinal doses have been administered for a lengthened period, arsenic causes more characteristic physiological actions than are described above. As regards the digestive organs, the following phenomena occur: A metallic taste; increased flow of saliva; nausea, vomiting of glairy mucus, epigastric pain, and soreness; diarrhoea, tenesmus, and sometimes dysenteric stools. As regards the circulatory and respiratory organs: the action of the heart becomes irritable and feeble, palpitations, cough, oppressed breathing, oedema of the eyelids, general oedema, and albuminuria occur. As regards the skin: itching of the eyelids, urticaria, eczema, pityriasis, psoriasis, and falling out of the nails and hair. As regards the nervous system: disorders of motility—trembling, stiffness, and contraction of the joints, disorders of sensibility, herpes zoster.

Notwithstanding the effects above described are so frequently observed to follow the use of arsenic, it is undoubtedly true that a certain degree of tolerance may be established when doses in themselves toxic can be taken with impunity. This state has been produced in a course of the legitimate administration of arsenic, and has been witnessed on a considerable scale among the arsenic-eaters of Styria and Southern Austria. The arsenicophagi begin the habit of arsenic-eating at an early age, and become habituated to the use of enormous doses. They find that this practice is serviceable in several respects: they improve in bodily condition, gain in breathing-power, and become stronger and more pugnacious, and also more salacious.

When arsenic is swallowed in sufficient quantity to cause the symptoms of acute poisoning, the phenomena produced are of two kinds— gastro-intestinal irritation and cerebral effects. The former is much the more common. The following are the symptoms of the gastro-intestinal form of acute arsenical poisoning: Burning at the epigastrium and radiating thence over the abdomen; violent and uncontrollable vomiting; great dryness of the mouth and fauces; intense thirst; intestinal irritation, bloody and offensive stools, retracted abdomen; strangury, priapism, suppression of urine or bloody urine, and in females menorrhagia; rapid and feeble action of the heart, oppressed breathing; great agitation and restlessness; shrunken features, cold breath; involuntary evacuations; collapse — consciousness being retained to the last. In the cerebral form of acute poisoning, without any symptoms of gastro-intestinal irritation, the patient is suddenly put into a condition of profound insensibility and coma, not unlike extreme opium narcosis.

Recovery from the effects of acute arsenical poisoning is rarely complete. For a long time afterward a considerable degree of gastroenteric irritability will persist, and life may at last be lost from the continued operation of this pathological state on the function of nutrition. An irritable state of the skin and stiffness of the joints may also continue for some time, and paralysis may supervene, accompanied with neuralgic pains, numbness, formication, etc.

The changes found after death in the gastro-intestinal mucous membrane are those due to an irritant: deep redness, erosions, ecchy-moses, and softening. These alterations are also produced when toxic effects are caused by the external application of arsenic. More or less redness of the tracheal and bronchial mucous membrane and congestion of the lungs have been observed. It must not be forgotten that arsenic has caused a fatal result without producing any gastro-intestinal lesions except some uncharacteristic redness. Fatty degeneration of the liver, kidneys, spleen, and other organs, has been observed in cases of acute poisoning, even when the symptoms have existed for a few hours. The icterode hue of the skin and the albuminuria which occur in the course of chronic arsenical poisoning are probably due to fatty degeneration of the liver-cells and of the renal epithelium.

Arsenic, although like other mineral poisons it tends to accumulate in the system, is nevertheless eliminated with considerable rapidity. If the patient survive a week after the ingestion of a toxic dose, it is difficult to detect it in the body after death. If the poison is retained and death ensues before elimination can take place, it undoubtedly retards putrefaction. Arsenic is eliminated by various organs—by the liver, intestinal canal, kidneys, and bronchial tubes—and some of the symptoms produced by it probably have their origin in the local effect of the poison on the channels of excretion.

The quantity of arsenic required to produce a fatal effect varies according to the state of the stomach and the susceptibilities of the patient. Ounces have been swallowed without producing even serious symptoms, because promptly rejected by vomiting. When the stomach is full of food, absorption is slow and vomiting is easily induced, and hence a toxic dose may not under these circumstances produce any of the phenomena of poisoning. A half-grain of arsenious acid has caused symptoms of poisoning (Taylor), and, according to the same authority, from two to four grains may prove fatal to an adult. Much depends on the idiosyncrasies of the individual, which, as has been stated above, differ greatly in different persons. These facts should not be forgotten in prescribing strictly medicinal doses of arsenical preparations.

From this general survey of the effects of arsenic, we may properly proceed to study the results of more minute investigations. Virchow has pointed out the similarity in the post-mortem appearances of arsenic and of cholera. The cholera-fungus of Klebs and the characteristic rice-water contents of the intestinal canal were not wanting to complete the resemblance. Hoffman has since fully confirmed these observations. Croupous exudations are sometimes encountered in the stomach and intestines, and crystals of arsenic have been found imbedded in the false membrane. This result is due to the action of arsenic when swallowed in powder, and is not produced when the poison is taken in solution (Filehne, Lesser). The gastro-intestinal inflammation, present in a large proportion of cases, is due in part to the local action of the arsenic, in part to its selective action, but this fact does not justify the statements of Böhm and Unterberger that a larger dose of the poison is required to destroy life by the intravenous injection than by the stomachal administration. Lesser holds with the authorities in general that arsenic, in common with other poisons, is more fatal by intravenous injection. In a small proportion of cases, as has been stated, gastro-intestinal inflammation does not occur, but the effects of the poison are expended on the nervous centers; several hours after the ingestion of a large dose, delirium, followed by coma, and convulsions come on, and with these albuminuria, occasionally urinary suppression. The relation of the attacks of eclampsia to the albuminuria has not been settled. In still other cases the gastro-intestinal disturbance, the rice-water discharges, the collapse, simulate the algid stage of cholera. The remarkable fall in the blood-pressure of the abdominal vessels produced by arsenic certainly throws light on these phenomena (Böhm and Unterberger).

The experiments of Sklarek have demonstrated that arsenic decidedly impairs sensibility, leaving the motor functions untouched. In the human subject, however, as the result of acute poisoning, and sometimes after the acute symptoms have subsided, certain paralyses develop. They may be preceded by numbness and tingling, and may be accompanied by contractures which disappear in curable cases, and remain permanently in incurable cases. The paralysis may be limited to a single member, and when several are thus affected the usual form of paralysis is paraplegia; but all four members may be thus disabled. The rectum and bladder are not affected (Christison). These clinical observations by Christison are confirmed by the researches of Ringer and Murrell, who have shown that Sklarek's statements were incorrect, and that motor paralysis precedes sensory paralysis in the frog poisoned by arsenic. (See Ponteland Poisoning Cases, "Lancet," September, I866.)

The effects of arsenic on the circulation are not the same in cold and warm blooded animals, for, according to Sklarek, in the former the action of the heart is slowed, then arrested, while in the latter the action of the heart persists after the cessation of respiration (Böhm and Unterberger, Lesser). This fundamental difference in the action of arsenic on the two classes of animals requires us to accept with. caution the observations made on the vaso-motor system of the coldblooded. It has been pretty definitely ascertained that arsenic causes a fall in the blood-pressure, which is especially strong in the abdominal blood-vessels (Böhm and Unterberger).

A fact of great importance, first ascertained by Saikowsky, is the fatty degeneration of the liver, kidneys, heart, and other organs. The case of Grohl and Mosler, reported in the same volume of Virchow's "Archiv" containing Saikowsky's paper, is confirmatory more or less completely of the observations in the latter. They found, as their figures well exhibit, fatty degeneration to a greater or less extent in the glandular epithelium of the intestinal canal, and less conspicuous evidences of the same change in the kidneys, the liver, and the muscular tissue of the heart. As the extent of the change is determined largely by the duration of the case, when death occurs in a few hours, or in a day or two, little alteration is discernible.

The effect of arsenic on the function of nutrition is as yet involved in doubt. It is a recognized fact that arsenic promotes constructive metamorphosis when administered in medicinal doses. It has been ascertained by Saikowsky that it arrests the formation of glycogen by the liver, and C. Schmidt has shown that it lessens the excretion of carbonic acid and urea. Although doubt has been thrown on these statements, they seem to be supported by the observations of Lesser on the temperature, which has been constantly and considerably depressed under the action of lethal doses. The effect of arsenic in lowering the functional activity of the respiratory center is a fact which supports the same view, for a diminution in the quantity of oxygen admitted to the blood must necessarily lessen the rate of oxidation. On the other hand are the adverse experiments of Kassel, a medical student under Prof. Gathgens, and Gathgens himself, which apparently demonstrate an actual increase in the amount of urea excreted. Arsenic has an anti-fermentative action; but it is not universally destructive of the minute organisms on the presence of which the various fermentations are dependent. Thus it is poisonous to Torula cerevisice and to some micrococci, but not to all, and it does not impair the activity of certain animal ferments, as pepsin, pancreatin, etc. (Johannsohn, Schafer, and Böhm). On the trophic system it acts as a depressant when taken in considerable quantity. The dust from, arsenical wall-papers has induced a cachectic state, accompanied by headache, vertigo, and tinnitus (Donkin). Aniline dyes fixed by a mordant of arsenic have excited ulceration of the nails, phlegmon of the hands, and anaesthesia and paresis of the extremities (Clemans).