The question has an intimate bearing on practical pharmacology. When we prescribe a cacodylate or an amylarsinate, we are not prescribing an arsenical treatment whose effects can be compared with those of an arsenide, an arsenite, or an arsenate. This fact is sufficiently indicated by the difference in the toxic doses of the different salts. Each variety of arsenical ion has its own special physiological and therapeutic properties. We do not expect to obtain the results of a ferruginous treatment from the administration of a ferrocyanide or a ferricyanide. Both contain iron, it is true, but neither possess the properties of the cation Fe+++, but rather those of the complex anion of which they form a part.
We have already said that most of the therapeutic, toxic, and caustic actions of an electrolyte are due to ionic action, and the substances can therefore have no toxic action unless they are dissociated. Many of the solvents employed in medicine, such as alcohol, glycerine, vaseline, and chloroform dissolve the electrolytes but do not dissociate them into ions, and these solutions therefore do not conduct electricity. Such solutions have no therapeutic action. With the absence of dissociation all the ionic toxic and caustic effects also disappear entirely, and only re-appear as the water of the tissue is able slowly to effect the necessary dissociation.
Carbolic acid dissolved in glycerine is hardly caustic and but very slightly toxic. We have met with several instances in which a tablespoonful of carbolized glycerine, in equal parts, has been swallowed without any ill effect, either caustic or toxic, whereas the same dose dissolved in water would have been fatal. This absence of dissociation has enabled the surgeon Mencière to inject carbolic and glycerine in equal proportions into the larger joints, the part being subsequently washed out with pure alcohol. Thus by employing vaseline, oil, or glycerine as a solvent, and avoiding the access of water, we are able to use electrolytic antiseptics in very concentrated form. Their action is brought out very slowly, as the water of the organism effects the necessary dissociation of the electrolyte.
Since all chemical, toxic, and therapeutic actions are ionic, they are proportional to the degree of ionic concentration, i.e. to the number of ions in a given volume. The only point of importance, that which determines their activity, whether chemical or therapeutic, is the degree of ionization or dissociation. For example, all acids have the same cation H+. They have all identical properties, but they differ widely in the intensity of their action. There are weak acids such as acetic acid, and strong acids like sulphuric acid. The stronger acids are those which are more thoroughly dissociated, and in which the ion H+ is very concentrated; whereas the feeble acids are but slightly dissociated, so that the ion H+ is less concentrated.
Paul and Krönig have shown that the bactericidal action of different salts also varies with their degree of dissociation, i.e. with the concentration of the active ions. They made a series of observations on the bactericidal action of various salts of mercury, the bichloride, the bibromide, and the bicyanide, on the spores of Bacillus anthracis. The following results were obtained from a comparison of solutions containing 1 gramme-molecule of the salt in 64 litres of water. With the bichloride solution, after exposure to the solution for twenty minutes, only 7 colonies of the bacillus were developed. After exposure to a similar solution of the bibromide the number of colonies was 34. The antiseptic action of the bichloride was therefore five times as great as that of the bibromide. The bicyanide of mercury, however, even when four times as concentrated, permitted the growth of an enormous number of colonies, showing that it had no appreciable antiseptic action whatever. Nevertheless, the proportion of Hg is the same in all the solutions, and if there were any difference one would naturally expect that the ion Cy- would be more toxic than Cl- or Br-. The real condition which varies in these solutions and determines their activity is the degree of dissociation. The whole of the antiseptic property resides in the ion Hg++. This ion is very
concentrated in the highly dissociated solution HgCl2, less concentrated in the less ionized solution HgBr2, and exceedingly dilute in the HgCy2, which is hardly ionized at all.
What is true of the bactericidal action of the salts of mercury is equally true of their therapeutic effect. It is a great mistake to estimate the medicinal activity of a solution of a salt of mercury, or indeed of any electrolytic solution, simply by its degree of molecular concentration. The important point is the degree of dissociation, which is the only true measure of its activity. In the intramuscular injection of mercury salts it is by no means a matter of indifference what salt we employ. A salt should be used such as the bichloride or the biniodide, which is easily dissociated. Other salts are often employed because they occasion less pain at the site of injection; but the pain is a sign of the degree of activity of the preparation. The pain, it is true, may be avoided by using a salt which is less easily dissociated, or in which the mercury is bound up in a complex ion, but by so doing we diminish the efficacy of the remedy. It is moreover quite easy to diminish, or even entirely to suppress, the pain, by using a very dilute solution of an active ionized salt. A one-half per cent. or even one-quarter per cent. solution of the bichloride or biniodide of mercury may be injected very slowly in sufficient quantity without producing the slightest discomfort. Local action depends entirely on ionic concentration. One drop of pure sulphuric acid will destroy the skin, whereas the same amount if diluted in a tumblerful of water will furnish a refreshing drink.