This section is from the book "Materia Medica And Therapeutics Inorganic Substances", by Charles D. F. Phillips. Also available from Amazon: Materia medica and therapeutics.
Readily obtained by decomposing any silver salt with hydrochloric acid, when it precipitates as a white caseous powder (horn silver): it darkens on exposure, and is soluble only in ammonia and in hydrochloric acid.
The Ammonio-chloride (not officinal) is an unstable salt soluble in water. The Chloro-albuminate, the iodide, and the double iodide of silver and potash are soluble salts that do not coagulate albumen. The hyposulphite of soda and silver is astringent and less irritant than the nitrate; the cyanide is said to be more readily absorbed.
Nitrate of silver, when taken into the stomach, forms with mucus and epithelium a thin pellicle, which, to some extent, hinders absorption. The chemical change which all silver salts undergo, more or less, when in contact with the gastric secretions, results in the formation of a double chloride of silver and sodium, and although ordinary chloride of silver is insoluble in water, this double chloride is readily dissolved by the gastric fluids; its combination with peptones is also soluble (Bogolowsky: Virchow's Archiv, xlvi., 18G9, and others). As chloride and albuminate it probably passes into the blood, and circulates with it, being retained in solution by the alkaline serum (Rouget), though Frommann thought that it separated in the molecular form (Archiv fur Path. Anat., 1859). Dragendorff considers that the chemical changes occur chiefly in the duodenum, and that the gastric juice being here neutralized by the bile, silver sulphide is ultimately formed: certainly, of unabsorbed silver compounds, the greater part passes off by the bowel as sulphuret, coloring gray or black the mucous membrane and the faeces. More of the salt will be absorbed if given in solution in distilled water on an empty stomach, than when given in pill in the ordinary manner. Riemer has shown that in pills (? bread) four-fifths of the silver nitrate is decomposed even before administration (Archiv der Heilk., xvi., 1875). The same observer also sought to prove that molecule,s of silver pass in a mechanical manner through the intestinal walls, but Fragstein could detect no absorption of freshly precipitated silver-chloride introduced into the intestine of frogs (Berlin. Klin. Woch., 1877). Orfila and Heller failed to find traces of silver in the blood after its administration; but Orfila and Panizza found it in the urine (Husemann), and Cloez isolated a globule of the metal from the collected urine of several patients at the Salpetriere. It has been found also in the liver and the bile, and some is eliminated by the cutaneous glands. Rozsahezzi found it in the intestinal contents after its hypodermic injection (Archiv Klebs, 1878).
The most important practical point is, that elimination of silver salts by any channel occurs but slowly, so that if they are taken continuously for a long time, the reduced metal becomes deposited in the tissues, giving them a dark-gray coloration, known as "argyria" The gums show the earliest indication of this condition by a bluish line (which is darker than that produced by lead), and parts exposed to light show the color more than others - thus the lunula of the nail (Falck), the eyes, the face and hands are affected early; the deposit is in the true skin (corium). Neumann has recently examined minutely a portion of the skin of a man who had partial argyria from frequent applications of nitrate to reduce large papillae on his tongue: dark granules of the metal were found in the upper part of the cutis, in the wall of the sweat-gland, in the connective tissue of hair-follicles, in sarcolemma, neurilemma, and the middle coat of vessels; none were deposited in the epidermis, the mucous layer, or the epithelial lining of hair-follicles or sweat-glands (Medical Record, 1877). That the coloring is partly due to the influence of light is shown by cases in which the viscera were seen to darken after exposure (Huet, Frommann, Fragstein), but the more active circulation of exposed parts is another factor in their coloration.
If the drug be stopped on the earliest appearance of affection of the gums, the general discoloration is not likely to occur. This was shown in the case of a woman who took nitrate of silver for two months - at first 1/5 gr., and later 2 gr. daily - swelling and redness of gums, with a purple line at the edges, appeared, and there was much tenderness of mouth with metallic odor of breath; but, on ceasing the medicine, these symptoms subsided (Bulletin de Therapeutique,v., 1871, p. 86). In other cases when large quantities have been taken, every part of the body has been affected. Van Geuns reports that a youth took about 1/2 gr. of the nitrate daily (with occasional intervals), from his fourteenth to his nineteenth year, none afterward: he died of phthisis at the age of thirty-five, and not only was the skin colored, but also the cerebral and spinal membranes, the laryngeal and bronchial membranes, the peritoneum, the papillae, and malpighian bodies of the kidney, the marrow, and the bones; the nervous, the hepatic, and other parts of the renal tissue were reported normal. Heynsius concluded on analysis that the dark granules were not chloride of silver (for ammonia did not affect them), nor oxide, but minutely divided particles of the reduced metal, and this conclusion is now generally accepted (Abstract, Dublin Quarterly Journal, August, 1858).
Charcot has recorded the presence of silver round the renal glomeruli and in the Malpighian pyramids, and Liouville has made a similar observation as to the kidneys, and also as to the choroid plexus of a patient who had taken 110 gr. in the course of nine months, three years before his death. Virchow recorded renal argyria after absorption from connective tissue. Several cases are quoted by Stille, by Sieveking, by Riemer, and others (Schmidt's Jahrbucher, ii., 1875, p. 295): many of them seem to have died of phthisis several years after the administration.
Argyria may even follow local applications of nitrate, as in the case of a girl whose throat was repeatedly cauterized - perhaps fifty times in the course of twelve months; she is said to have swallowed the products (Gazette de Paris, xxviii., 1874). It has occurred also after tracheotomy, the wound having been pencilled "for a long time" ("Dictionary Encyclopedia," v., vi.), and in a woman after the continued use of a nitrate pomade for dyeing the hair.
It is important to ascertain, if possible, what quantity of the drug is liable to produce coloration, and the time during which its use may be safely continued. The actual amount deposited is certainly very small: Versmann found only 0.047 per cent. in the liver in a well-marked case, but Krahmer estimated that there must be the residue of at least 1 oz. of the salt to cause discoloration: from 3 to 5 oz. are mentioned as the quantities taken in several instances, but, judging from Liouville's case, it is probable that less than 1 oz. might suffice. Six weeks has been named as a safe limit of time for the continued administration of the drug, and I should think it almost impossible for any ordinary dose to produce bad results within that period.
The sulphide was the salt used in the first authentic recorded case of coloration (Weigel): the iodide is said to be free from this risk, and no case has been traced to it, but Husemann considers this as accidental: the double iodide of silver and potash is also regarded as less liable to be deposited (Delioux).
If moistened nitrate of silver be applied lightly to the skin, it combines with albuminous material, and leaves a white stain, which soon darkens on exposure to air or light, because of its reduction to metallic silver; the darkened epidermis peels off in a few days' time. Strong applications, such as the moistened stick, or solutions of 1 to 2 dr. in the ounce, cause more or less severe burning pain, and, in delicate skins, vesication. On mucous membranes, or moist denuded surfaces, a whitish layer is formed by combination with chlorides and albuminous secretion: this layer soon becomes gray and then dark, and when it peels off may leave the part tender. Applied to a suppurating surface, the solid nitrate combines with the purulent secretions to form a grayish layer, stimulates the healing process, and causes some burning pain and redness near the part: when the superficial eschar falls, as it does in twenty-four to forty-eight hours, fresh and healthy granulations are usually found on the wound. The action cannot extend deeply because of the pellicle which is formed, and the so-called "caustic" effect of nitrate of silver must be distinguished from that of destructive agents, such as potash or acids, for it is produced by coagulating and hardening organic tissues, rather than by destroying them. The affinity of the salt for albumen, and its forming with it an insoluble compound, explain most of the local effects of the nitrate.1
A solution of about 20 gr. per ounce brushed over a moderately inflamed part not only discolors it, but reduces its size, controlling inflammation, and constringing the blood-vessels. The conjunctiva has sometimes been discolored by continuous use (to it) of medicinal drops, and in this and other very sensitive parts, such as the schneiderian, buccal, or urethral membranes, much pain, irritation, and increased secretion follow the use of strong solutions. Weak solutions (1 to 3 gr. in 1 oz.) have an astringent and slightly stimulant action, and do not cause pain except to a delicate membrane like the conjunctiva. Silver solutions possess, also, antiseptic power, in degree somewhat proportionate to their strength, and dependent in part, though not wholly, on coagulation of albumen.