In itself, calomel can scarcely be considered as irritant. This would seem to be a necessary consequence of its insolubility. Hence its want of acrid taste, and the absence of all evidence of irritation, for some time after it has been taken into the stomach. The probability is that, simply as calomel, it is perfectly bland when in contact with the alimentary mucous membrane. But, in consequence probably of the presence of chlorides in the contents of the canal, it slowly forms small portions of the soluble double chlorides of mercury and the alkaline metals, as shown by Mialhe (see page 303), which are sooner or later absorbed, but, while still in the canal, must prove somewhat irritant to the mucous surface. it is not impossible that calomel may in this way, in some degree, act as a cathartic; but I believe that its influence on the bowels depends chiefly on another cause.

It is very rare that the stools produced by calomel are not highly bilious; and the most probable view of its purgative action is, I think, that the bile which it causes to be poured into the duodenum is the real purgative. We know well that an excess of bile in the bowels, resulting from morbid causes, purges, and not unfrequently also vomits, as in bilious diarrhoea and cholera morbus. its presence in the same place, under the influence of calomel, must be followed by the same results.

It is an interesting question how calomel acts in producing this increase of the bilious secretion. Some suppose that it is merely by irritating the orifices of the biliary ducts, and the neighbouring mucous membrane, upon the general principle, that an irritation of the surface, upon which the outlet of a gland opens, causes an increased action of the gland, as food in the mouth causes an increased flow of saliva. But, if this were the true mode of action, other irritants should have the same effect; and gamboge, elaterium, and other drastics should be more powerful cholagogues than calomel; whereas it is very doubtful whether they produce any specific effect whatever on the liver. A much more reasonable supposition appears to me to be, that the calomel, as fast as rendered soluble in the stomach and bowels, is taken up by the radicles of the portal veins, and thus conveyed immediately to the liver. it has been proved, by experiment, that foreign substances in the stomach and bowels find a much more ready entrance into the circulation, through the portal veins than through the lymphatics or lacteals; and there can be little doubt that this is the case with the mercurial. Distributed, then, through the liver, and brought into immediate contact with the cells of the acini, it excites these to increased action, and thus produces the great excess of the bile characteristic of its operation.

We can thus account for the fact that calomel is much less apt to salivate when it purges. it might be supposed that this was owing to the discharge of the calomel itself from the bowels, and, no doubt, this is one cause; but I believe a stronger is that, when absorbed and conveyed into the liver, it is thrown off by the secreted bile, and thus prevented from gaining access to the system. When the liver does not respond to this influence, either from the minute amount of the mercurial absorbed, or from its own insusceptibility, the medicine passes onward into the general circulation, and affects the system. When calomel does not purge, there is a want of responsive action of the liver, and hence it often salivates. Some persons are not readily purged by the medicine, but are proportionably more easily ptyalized; others are purged very readily, and by minute quantities; and I have noticed that it was difficult to bring the systems of the latter under the influence of mercury given by the mouth.

The excessive susceptibility occasionally exhibited to an irritant influence on the stomach and bowels, already alluded to, may be readily explained upon these principles. in these cases, it may be remembered that the irritation is not felt until several hours after the medicine has been taken. This would not be, if the irritation were direct on the mucous membrane. When the vomiting, purging, and spasmodic pains come on, the matters discharged are highly bilious, and the phenomena almost precisely like those of severe bilious diarrhoea or cholera. it is thus the acrid bile that produces the irritation. The fact, then, appears simply to be, that, in these persons, the liver is extremely sensitive to the action of the absorbed mercurial, so that a quantity which, in an ordinary individual, would in no degree sensibly affect the secretory function, in them acts on it powerfully. I have already stated that half a grain of calomel will in these persons almost always act as a laxative, with bilious stools; and it is in patients of this kind, that I have repeatedly failed in any attempts at salivation through the alimentary canal.

We can also, upon this principle, understand why the mercurials, applied externally, do not as a general rule purge. The medicine, upon entering into the circulation, does not pass through the liver, and reaches that organ only as it does all other parts of the body, through the arteries. The quantity, therefore, carried into the liver is insufficient materially to affect its secretory function; which, moreover, may be less responsive to excitants reaching it through the general circulation, than to those brought to it by the portal vein, which probably supplies it mainly with material for secretion.

Another important fact is explicable upon the principles here laid down. it has been stated that, beyond a certain dose of calomel, which, however, may vary for different individuals, and for the same individual at different times, an increase of the medicine is not attended with an increase of effect. Thus 10 or 15 grains will act as vigorously as a drachm, or an ounce. it will be recollected that only that portion of the calomel which is dissolved in the alimentary canal really operates; whether by a direct action on the membrane, or through the liver by absorption. Now the quantity dissolved is limited, as proved by Mialhe, by the amount of the chlorides present in the canal. if this is small, no matter how large the dose of the calomel, the effect will be small; if large, the effect will be proportionate to the quantity, until the whole converting power of the chlorides is exhausted, after which the calomel becomes inert. Thus, if there be any chloride present, a small dose of calomel will operate to the full extent of its quantity; while a larger quantity will be limited in its effects by the amount of chlorides; and as these may be supposed to differ in different persons, and in the same person at different times, it is understood how the greatest effect of the calomel must also vary.

The comparative insusceptibility of children to the purgative operation has been explained in the same way. it is supposed that, from the character of their diet, or other cause, there is apt to be less of the chlorides in their stomach and bowels than in those of adults. There is consequently less of the calomel rendered soluble, and proportionably less purgative action.