This section is from the book "Materia Medica: Pharmacology: Therapeutics Prescription Writing For Students and Practitioners", by Walter A. Bastedo. Also available from Amazon: Materia Medica: Pharmacology: Therapeutics: Prescription Writing for Students and Practitioners.
Nausea, vomiting, diarrhea, and colic are commonly seen from the use of arsenic. These effects seem to be produced after absorption, for they occur late, and even when the drug is administered hypodermatically. Experimentally, after large hypodermatic injections, there is edema of the intestine from increased permeability of the capillaries, with degeneration and exfoliation of the intestinal epithelium. Arsenic-eaters claim that it helps the appetite.
Large therapeutic doses tend after a few days to produce edema of the skin and alimentary tract, as shown by puffinness about the eyes and other parts of the body, or by general edema, nausea, vomiting, or diarrhea. This is due to increased transudation of serum, from heightened permeability of the subcutaneous and submucous capillaries. In some cases petechial (capillary) hemorrhages are seen.
In chronic poisoning there may be fatty degeneration of the heart and arteries.
It is upon the blood or blood-making organs that arsenic seems to exert its most valuable therapeutic effects. The normal bone-marrow consists essentially of erythroblastic and leukoblastic elements and fat cells. When arsenic is administered for long periods to young growing animals, the bone-marrow becomes more vascular, with increase in the leukocytic elements, decrease in the fat, and little if any change in the erythrocytic elements (Charteris, 1903). There is no change in either the number of red cells or the percentage of hemoglobin in the blood. Besredka, from sublethal doses in rabbits, noted a temporary diminution of the leukocytes in the blood, followed by a polymorphonuclear leukocytosis.
In the Manchester epidemic, in which over 3000 cases of arsenic poisoning occurred from arsenic in beer, the cases which came to postmortem showed these changes. But some of the most pronounced cases showed extensive degeneration of the marrow-cells and profound anemia; and this corresponded with Charteris' findings that "from repeated doses large enough to cause cachexia and emaciation in rabbits, the bone-marrow undergoes hyaline degeneration, and this is accompanied by decrease in the red cells and hemoglobin."
The tendency of arsenic is, therefore, to increase the leukoblastic elements of the bone-marrow and the leukocytes in the blood; but in severe chronic poisoning, to induce degeneration of the marrow-cells, wasting, and profound anemia.
In pernicious anemia there is an increase in the erythroblastic elements of bone-marrow, associated with increased destruction of red blood-corpuscles (hemolysis); in leukemia, there is an increase in the leukoblastic elements. In both of these conditions arsenic is employed, at times with benefit, and it may be that it acts on some yet undiscovered toxin or parasite. It scarcely seems to be curative, however, for its effects do not last. In chronic malaria, also, there is a destruction of red cells which may be more or less checked by arsenic.
Brown and Pearce (1915) tested 60 arsenic compounds and found that all in toxic amounts caused congestion and hemorrhage in the suprarenals, alterations in the lipoid content, cellular degenerations and necroses, and reduction in chromaffin. In the kidneys they obtained varying effects according to the compound used. Arsenous acid produced a vascular nephritis, arsacetin a tubular nephritis, while salvarsan and neosalvarsan produced a vascular nephritis with some tubular changes, and atoxyl and arsenophenyl-glycin a tubular nephritis with some vascular changes.
Long-continued administration lessens the activity of the liver, so that it forms less glycogen and has less power of oxidation. This shows in the urine by increased amounts of uric acid and ammonia, and the presence of leucin, tyrosin, and sarcolactic acid, the total nitrogen of the urine not being much changed. There may be a swollen liver and jaundice. After a fatal dose arsenic is usually found most abundantly in the liver.
Considerable doses not only cause degenerative changes in the bone-marrow, but have a strong tendency to produce fatty degeneration in the liver, kidneys, heart, arteries, capillaries, the epithelium of the lungs and alimentary tract, and striated muscle and skin (dermis and epidermis).
In growing animals of poor nutrition it tends to bring about an increase in the density of bone, the cancellous portion being encroached upon by the increasing thickness of the hard bone. This may be due to the increased vascularity of the bone-marrow. In adults there is probably no effect on bone.
That it promotes the nutrition of the skin and epithelial tissues is a general belief, as indicated by the sale of arsenic complexion tonics, by the frequent administration of Fowler's solution to horses to improve their appearance, and by the use of arsenic in chronic skin diseases. Thomas Oliver gave a dog with short, stubby hair 1 grain a day, and the hair became sleek and long (Allbutt's System of Medicine).
It is excreted in the urine and to some extent in the feces. Traces may appear in the gastric juice, the bronchial mucus, the sweat, and the milk. It is reported as appearing in the stomach after administration by rectum (Kandikoff) or hypodermatically. Its elimination is very slow, and traces may be recovered two or three weeks after its administration has ceased.
Among the mountaineers of Styria, Hungary, and certain parts of the Punjab there are a number of persons known as "arsenic-eaters." They live to old age and have no symptoms attributable to arsenic except perhaps catarrh of the upper respiratory passages. Knapp and Buchner saw a man who had had the habit for thirty-six years take 2.6 grains (0.175 gm.) of orpiment (arsenic sulphide). Knapp administered 7 grains (0.45 gm.) of arsenic trioxide to one of the arsenic-eaters of Graz without any effect. Maclagan saw a man take 6 grains (0.4 gm.). It is taken about once or twice a week, and is said to act somewhat like an intoxicant, increasing combativeness, stimulating the sexual appetite, and giving a feeling of strength and general well-being.