Ferri Et Quiniae Citras - Citrate Of Iron And Quinine

Preparation

By dissolving freshly precipitated peroxide of iron and quinine in solution of citric acid, adding ammonia and evaporating to dryness at moderate temperature. The product is a triple citrate of iron, quinine, and ammonium, and contains both a ferrous and a ferric compound.

Characters And Tests

Occurs in greenish-yellow scales which become darker by age; they are at first deliquescent and very soluble in cold water, but become less so on exposure to light; it has a chalybeate, and at the same time a bitter taste. It should contain 20 per cent. of Fe2O3, and 16 per cent. of quinia, but the proportion of the latter varies, falling sometimes to 4 per cent. The solution is slightly acid: soda precipitates the reddish-brown peroxide Fe2O3, and ammonia a white deposit of quinia.

The citrate of quinine with iron and zinc, and with iron and strychnia, and many other double compounds, have also been prepared in granular effervescent form.

Absorption And Elimination

If, in former times, the absorption of any medicine was commonly denied, with us the absorption of all is now commonly accepted as a necessary condition of their acting on the system, and yet the absorption of medicinal doses of iron has been doubted by some eminent men, and mainly because chemists, after giving the drug to animals, have often failed to detect an increased quantity of it in the vena portae, and have sometimes failed to find any in the urine.

On appeal to the clinical evidence of improved color and tone after the use of iron, the objectors attribute such results to a local tonic action upon the gastric mucous membrane leading to improved digestion; but besides that iron salts have often rather a contrary effect, it would not, in any case, account for all that we see, nor for the chemical changes produced in the blood. It seems more reasonable to allow that the medicine, which we can prove to be, to some extent, soluble in the gastric fluids, should be really absorbed, at least to the extent of its solubility. From most articles of diet certainly traces of iron are absorbed, as we know from detecting the metal in the blood and tissues: if there be some failure in the supply, or in its assimilation, then color and strength fail (just as when iron is removed from a soil, white vegetables and chlorotic oats spring up from it), and conversely health and color usually return when suitable ferric preparations are added to the nutriment or to the soil. Definite facts in proof of absorption are such as the following: Tiedemann and Gmelin administered to a horse about 6 dr. of sulphate of iron, and found an increased amount of the metal in blood from the splenic and hepatic veins, and in some experiments, in the lymph also. Manghini recorded a distinct increase in the amount of iron in the blood of dogs when he added the metal to their food (Bayle: "Biblio. de Therap.," v., iv.). Wohler, though he failed to detect iron in the urine after giving various preparations of it to animals, yet succeeded in detecting it by means of tincture of galls in the urine of patients taking chalybeate waters; he also noted its occasional presence in calculi and in urinary sediments (Treviranus: Zeitschrift, vol. i., 1824, p. 302). Quevenne, in his careful and admirable memoir, says that only a minute quantity can be detected in normal urine, but that after medicinal doses the amount is increased slightly: in the bile and faeces the increase is greater (Bou-chardat: Archives de Physiol., etc., No. 2, October, 1854). Schroff found that when small doses were given to animals, elimination by the kidneys was evident, and began sooner, and continued longer, than after larger doses; he recorded also the curious fact (and Becquerel corroborated him), that even during the use of equal and continued doses, the amount passed in the urine was subject to much fluctuation, implying that that secretion was not the best gauge of absorption. Bence Jones speaks of detecting iron in the urine within ten minutes of the administration of a soluble salt, also of the rapid diffusion of another portion of it into the textures and corpuscles (Lectures, Medical Times, ii., 18G0, p. 245), and Delioux de Savignac affirms that it may be readily and frequently found in all the secretions (Gazette Med. de Paris, April 25, 1874). Bistrow verified the presence of nearly double the ordinary amount of iron in the milk of a goat after the administration of 15 to 40 gr. of lactate of iron; elimination of increased amount began in the milk forty-eight hours after giving the dose, implying a slow absorption or long detention in the tissues (Husemann). In Dr. Marcet's classical case of a man who had swallowed several knives, particles found in the bile were attracted by the magnet, and that liquid contained more than double the normal amount of iron ("Philos. Trans.," xii.).

More modern observations are those of Rabuteau, who passed through a tube varying amounts of protochloride of iron into the stomach of dogs, which were killed a few hours afterward; the stomach was found to contain only a small amount of the compound, the intestine somewhat more, but the greater part had passed into the blood, which was found on analysis to contain, in these cases, distinctly more iron than under ordinary conditions (Journal de Therapeutique, 1875). In another series of experiments he injected the same salt directly into a vein; it did not cause coagulation - on the contrary, it increased the fluidity of the blood, and yet no increased amount of iron was found in the urine. The greater part of what was injected passed away by the intestine, proving again that failure to find the metal in the urine is no proof of its non-absorption into the blood; similarly, the protoxide was injected in large doses by Papi, and was found unchanged in bile and faeces, but not at all in urine (Husemann).

I cannot doubt that a true absorption of iron compounds occurs from the gastro-intestinal mucous membrane, though it may be often partial and incomplete, and is certainly rather slow and limited: it varies according to the preparation used, the reaction of gastric juices, and the state of the stomach as to food, etc. Woronichin showed that while chloride of sodium promoted the assimilation of iron, chloride of potassium much increased its elimination (Wiener Med. Woch., ii., 1868), and Brucke demonstrated in rabbits, that after a certain period the system, or more accurately the corpuscles, became so charged with the substance that it was no longer retained in the tissues, but passed almost wholly in the urine (Husemann).

With reference to the absorption of iron from the cellular tissue, C.

Bernard performed a well-known experiment, injecting ferro-cyanide of potassium into the thigh of an animal, and solution of lactate of iron into its neck; the spot in the thigh remained unchanged in color, but the neck quickly showed blue, implying that the cyanide had been taken into the circulation, and so reached the iron, but the lactate of iron had not travelled to the cyanide. Soluble salts, however, are certainly absorbed from wounds, and from the bared skin (Husemann), and recently, good effects have been obtained from hypodermic injection of a double salt (pyrophosphate and citrate) "in pernicious anaemia," after failure of ordinary means (Huguenin: Schmidt's Jahrb., Bd. clxxiii., 1877). The observations of Hamburger as to the absorptive powers of the vagina (tampons soaked in iron solution being introduced into it) were vitiated by his confining analyses to the urine - elimination by that secretion being, as we have seen, very uncertain - and he could come to no definite conclusion (Prager Vierteljahrschrift, 1876, p. 145).