This section is from the book "A Text-Book Of Pharmacology, Therapeutics And Materia Medica", by T. Lauder Brunton. Also available from Amazon: A text-book of pharmacology, therapeutics and materia medica.
General Actions of Heavy Metals. - The. heavy metals form compounds with albumen, known as albuminates. These are sparingly soluble, and in consequence of this, white of egg is a useful antidote in poisoning with heavy metals. Albuminates of copper have been obtained by Harnack in which the proportion of copper is definite, and is either 1.35 or 2.64 per cent. On account of their affinity for albumen the heavy metals combine with the albuminous constituents of the tissues, and act as powerful astringents (p. 349), irritants (pp. 341 and 395), or caustics (pp. 344 and 346), according to the strength of the application. Their action is comparatively slight when they are applied to the unbroken skin, as the epidermis forms an obstacle to their action, but it is strongly marked where the epidermis is absent, as in wounds or ulcers, and on mucous surfaces where the epithelium is soft. In addition to their astringent action on the fluids and tissues, two metals - lead and silver - cause contraction of the blood-vessels (p. 349). In considering the action of the heavy metals belonging to this group and those belonging to Classes III.-VIIL, on the organism, it is necessary to distinguish carefully between (1) The local action upon the surface of the body or upon the alimentary canal, with the reflex effects upon the nervous, respiratory and circulatory systems consequent on this local action, and (2) The effects produced on the various organs of the body by the metal after its absorption. Thus, a large dose of corrosive sublimate when swallowed may produce the ordinary symptoms of irritant poisoning, causing vomiting and purging by its local action on the stomach and intestine, and producing reflexly general collapse with feeble circulation and respiration. Yet if the treatment be prompt, none of the metal may be absorbed, and thus the symptoms which would be produced by its action on the various organs when carried to them by the circulation may be absent.
In considering the effects produced by a metal after its absorption, we must remember that the nature of its action differs according to the quantity present in the blood at any one time, and that this quantity depends on the relation between the rapidity of absorption and excretion (p. 39).
The proportion between absorption and excretion depends greatly on the channel of introduction, and therefore the same drug may produce quite different effects according to the mode of its administration. Thus solution of perchloride of iron, when injected directly into the veins, will cause almost immediate death from coagulation of the blood. Other salts of iron which have no coagulating action, if injected into the circulation, produce paralysis of the central nervous system and of the vasomotor nerves, causing loss of voluntary motion, an enormous fall of the blood-pressure, and death. When injected subcutaneously iron is absorbed, but it enters the blood less rapidly than when injected into the veins, the quantity present in the blood at any one time is less, and these symptoms are not produced. Nevertheless absorption takes place from the subcutaneous tissue so rapidly that enough iron enters the blood to produce a toxic action. But this action, instead of affecting the nerves, is chiefly exerted on the excreting system, and inflammation of the kidneys occurs. When taken into the intestinal canal iron is absorbed very slowly, and only a very small quantity appears in the urine. It is hard to say whether the slight headache which is apt to come on from the administration of iron is due to the direct action of the metal on the nerve-centres after its absorption, or is merely reflex and due to the action of the metal on the intestine. No injury is done to the kidneys of healthy persons, though the effect of the iron upon these organs may be manifested by the diminution of albumen in cases of renal disease.
The form in which metals are absorbed from the intestinal canal is probably that of albuminates, or, perhaps, more properly, of peptonates.
The only heavy metals which are rapidly absorbed from the healthy intestinal canal are lead, mercury, and arsenic. Copper, zinc, silver, tin, iron, manganese, nickel, and cobalt are absorbed very slowly indeed. This is shown by the fact that when given internally only mere traces of them appear in the urine. That their absence from this secretion is due to non-absorption, and not to their retention in the blood or tissues, is proved by the fact that when they are injected subcutaneously they pass readily through the kidneys.
Contrary to one's expectation, it has been found that metals are much more readily absorbed by the gastro-intestinal mucous membrane when it is in a catarrhal condition than when it is in a healthy state. When large doses of metallic salts are given at once they are very apt to produce acute catarrh of the intestinal canal, and they are then readily absorbed, and appear in large quantity in the urine. If small doses are given at first, instead of large ones, they may be gradually increased without producing any catarrh, and then absorption into the blood and excretion by the urine does not occur, or only to a slight extent, although the dose finally reached may be large.
The therapeutic bearing of this fact is that if we wish to affect the kidneys by metallic remedies, e.g. by iron in cases of albuminuria, the best method of administering the remedy is to begin with large doses at once.
After absorption into the blood the metals probably remain, to a great extent, if not entirely, in the plasma, and do not become combined with the corpuscles, or only to a very slight extent.1
They are carried to all parts of the body, and probably unite with certain tissues. They remain in combination with the tissues for a greater or less length of time, modifying their nutrition and functional activity, and then, being again set free, they become excreted.