There are many official preparations of iron (ferrum), but a knowledge of only seven or eight will give a good equipment for iron therapy. (Those made in our laboratory were the syrup of ferrous iodide, the solution of ferric chloride, the tincture of ferric chloride, the liquor ferri et ammonii acetatis, Blaud's pills of ferrous carbonate, and the arsenic antidote of ferric hydroxide with magnesia.)

There are four main uses in medicine for preparations of iron, as follows:

1. Disinfectant

Ferrous sulphate (copperas), for sinks, water-closets, cess-pools, etc. It is cheap, but not very effective.

2. Astringent

The ferrous and ferric salts of the mineral acids, especially the sulphates, the subsulphates, and the chlorides, precipitate protein, are strongly astringent, and coagulate the blood. They are also irritant. A mixture of equal parts of the tincture of ferric chloride, glycerin, and water is a favorite application in sore throat; it is astringent and irritant; it may attack the teeth. The use of these astringent preparations in nose-bleed and other small hemorrhages (the styptic action) results in a dirty coagulum and irritation of the tissues, and it has practically been abandoned. Liquor ferri chloridi, liquor ferri subsulphatis (Monsel's solution), and liquor ferri tersulphatis are official.

3. Arsenic Antidote

The freshly precipitated ferric hydroxide changes the active arsenows preparations into the comparatively inactive and insoluble arsenic compounds of iron. Amy gives the reaction with arsenous acid as: 3As2o3 + 2Fe(OH)3 = 2Fe(As02)3 + 3H2O. Ferric hydroxide as an antidote may be administered in large quantity, after which it must be washed out of the stomach without delay to remove the arsenic compound formed.

Ferri hydroxidum cum magnesii oxido is made with a mixture of magnesium oxide and water, and may be given freely.

MgO + H2O = Mg(OH)2 Fe2(So4)3 + 3Mg(OH)2 = 2Fe(OH)3 + 3MgSo4 id) The Salts of Organic Acids. - These are the ferric acetate, citrate, and tartrate. U. S. P. preparations are: Liquor Jerri et ammonii acetatis (Basham's mixture), dose, 2 drams (8 c.c.); and the soluble double alkaline salt, iron and ammonium citrate. The iron and ammonium tartrate, and iron and potassium tartrate, dose, 4 grains (0.25 gm.), the citrate of iron and quinine, dose, 4 grains (0.25 gm.), containing \ grain of quinine, and the citrate of iron and strychnine, containing 1 per cent. of strychnine, dose, 2 grains (0.13 gm.), are no longer pharmacopceial.

It is not necessary to wash out the magnesium sulphate.

Ferric hydroxide may also be made by precipitating the solution of ferric sulphate or ferric chloride with ammonia water, filtering, and washing the precipitate with water to remove the ammonium sulphate.

4. Hematinic, tending to increase the hemoglobin content of the blood. The hematinics may be separated into six varieties:

(A) Metallic Iron (Ferrum Reductum; Reduced Iron)

Dose, 1 grain (0.06 gm.). It is a fine, grayish-black powder, made by reducing ferric oxide with hydrogen. It consists of not less than 90 per cent. pure iron, and requires acid in the stomach for its solution.

(B) The Inorganic Ferrous Salts

They are: The carbonate in the saccharated carbonate, massa ferri carbonatis (Vallet's mass), and pilula ferri carbonatis (Blaud's pills); the iodide in pills of ferrous iodide and syrup of ferrous iodide, dose, 15 minims (1 c.c.); the sulphate, dose, 3 grains (0.2 gm.); the dried sulphate, dose, 2 grains (0.13 gm.); the latter in pills of aloes and iron, each containing 1 grain (0.06 gm.).

(C) The Inorganic Ferric Salts

These are the chloride, dose of the tincture, 5 minims (0.3 c.c.); and the phosphate, dose, 4 grains (0.25 gm.). The elixir and the syrup of the phosphates of iron, quinine, and strychnine, dose, 2 drams (8 c.c.), are no longer pharmacopceial. These mineral salts are astringent, irritating to the stomach, and constipating. In liquid form they tend to blacken the teeth and to injure the enamel. To protect the teeth the dose should be well diluted, taken through a tube, and followed by rinsing the mouth. The tincture of the chloride contains free acid and is especially destructive to the teeth.

The salts of this group do not readily dissociate, so they do not readily precipitate proteins. Hence they are less irritant, less astringent, and less constipating than the salts of the mineral acids. Their solutions do not corrode the enamel of the teeth.

The citrate in 5 per cent. solution has been used hypoderm-atically in dose of 1 grain (0.26 gm.) with reported rapid effects.

(e) Artificial Protein {or Organic) Compounds. - Albuminates, peptonates, etc. Ovoferrin is a liquid purporting to be made from the white of egg; ferratin, a preparation claimed incorrectly to be the natural iron compound of the pig's liver.

(/) True "organic" or "masked" iron, sometimes spoken of as food iron, as in hemoglobin or yolk of egg.

Absorption

To prevent irritation of the stomach, iron preparations are regularly administered after meals, and mostly form the ferrous chloride or albuminate in the stomach. On passing to the duodenum, the chloride or sulphate probably changes to the carbonate. After a meal containing an added iron salt, granules of iron are found in the epithelium and leukocytes of the duodenal mucous membrane and in no other portion of the alimentary tract (Macallum). But after an iron-nuclein compound, Cloetta found it also in the membrane much further down the small intestine. It enters the blood probably either as the albuminate or carbonate. There seems to be no essential difference in absorbability between the inorganic and organic forms of iron. The spleen does not exert any constant or important influence on the iron metabolism. Even in the absence of the spleen a sufficient supply of iron results in normal blood conditions.

A medicinal dose of an iron salt is 3 to 5 grains, but, as has been shown by severing the intestine above the cecum, almost all of this passes through the alimentary tract unabsorbed. Some of it forms the sulphide, and this may give a dark or blackish color to the feces. Iron that is absorbed but does not enter into hemoglobin or some other natural organic compound is a foreign substance and is poisonous.

The Absorbed Iron

This passes into the portal blood and perhaps slightly into the lymph, and is soon found deposited in the spleen and mesenteric lymph-nodes and slightly in the liver cells and the cells of the convoluted tubules of the kidney. Later it is found in greatest abundance in the bone-marrow and liver, and still later appears in the epithelium of the colon and rectum, where it is excreted into the feces. Of the iron excreted by normal persons under normal conditions, about nine-tenths is excreted in the feces, and one-tenth in the urine. Practically all the medicinal iron is excreted in the feces. A portion of the iron of the liver is synthetized into organic compounds (ferratin, etc.), ready for conversion into hemoglobin, and the rest is doled out for excretion. There is no increase in the amount of iron in the bile.

Effect On Blood

Normally, the whole adult human body contains from 40 to 55 grains of iron, enough to make a 2-inch nail. The ordinary diet contains 1/12 to 1/6 grain (5 to 10 mg.) of iron per day, this minute amount being sufficient to maintain the iron equilibrium of the body. During the growing period more iron is necessary. In human milk, between the third and twelfth days of lactation, Cameron found 21 mg. of iron in 100 c.c.; while in mixed cows' milk Bunge found 3.5 mg., and Van Slyke only 1 mg. in 100 c.c. Krasnogorsky found the iron of milk more readily absorbed than that of egg-yolk or spinach.

For over a month Charteris (1903) gave normal rabbits a daily hypodermatic of 1/2 to 1 grain (0.03-0.06 gm.) of an albuminate of iron. They maintained health and gained weight. There was no essential change in the bone-marrow except a slight increase in the density and vascularity of the leukoblastic elements. But healthy mice fed on cheese and iron regularly contained more iron in their tissues than control mice fed on cheese alone, and healthy goats fed on milk and iron more than goats fed on milk alone. Therefore, in health, though the administration of iron results in some accumulation of iron either free in the blood or stored up in the liver, spleen, etc., it is not followed in adults by any notable increase in either the hemoglobin or the red cells, and the iron is in a sense a foreign body; that is, it does not go to form blood, and there is no plethora established. But after bleeding, animals have been shown to utilize iron that was given them, and in many human cases with hemoglobin below normal its administration seems to be followed by a greater increase in both the hemoglobin and the red cells than comes from the food alone. In these cases it is possible that "under the stimulus of iron the blood-forming organs become active in the synthesis of hemoglobin" (von Noorden). Kleinschmidt found that growing dogs had a much greater power than adults to utilize iron given with the food.

Hemoglobin itself, as in raw blood or uncooked meat, is converted by the gastric juice to acid hematin, and when taken by man is believed to be mostly unabsorbed. It has been ascertained that I c.c. of blood by mouth will give a test in the feces. However, Halliburton's experiments with raw blood on rats fed on an otherwise iron-poor diet, showed a slight increase in the red blood-corpuscles and hemoglobin of the blood, and the presence of absorbed iron in the cells of the duodenal mucous membrane.

Incooked blood, as in cooked meat, the hemoglobin is changed and is absorbed more readily, but even then not readily.

Toxicology

In excessive amounts iron may produce nausea, vomiting, constipation, and headache. Dixon says that if it is administered intravenously it is as toxic as arsenic. In very large quantities the irritant inorganic salts may cause great irritation of stomach and bowels, with collapse. There is no satisfactory evidence that excess of iron has any power to increase a hemorrhagic tendency or to bring on plethora.

Therapeutics

The therapeutic classification given above indicates its. uses. As a hematinic it may be employed in all conditions with diminished hemoglobin. Its most prompt effects are seen in chlorosis, but good results may also follow its use in the secondary anemias. It is best given in conjunction with appetizers, tonics, laxatives, etc., according to need. In nephritis the anemia is often treated with iron, especially Basham's mixture, but there is no satisfactory evidence of any direct effect upon the kidneys or upon the excretion of albumin. It has been employed also in functional albuminuria, and there is a traditional belief that it will cure this condition. The citrate has been used hypo-dermatically, in 5 or 10 per cent. solution, in dose of 1 grain (0.06 gm.) daily. It is readily absorbed.