There are three different methods of applying drugs by the skin which are well recognised, these are :1. Epidermic, to the skin covered by epidermis.

2. Endermic, to the skin denuded of epidermis.

3. Hypodermic, to the subcutaneous cellular tissue.

Epidermic Application. - Remedies are applied to the unbroken skin chiefly for their local action on the part to which they are applied, or their reflex action through the nervous system on more distant parts. The epidermic applications are comparatively rarely used as a means of introducing drugs into the system, for the epidermis opposes such an obstacle to absorption, that it takes place slowly and with great difficulty.

In some of the lower animals, such as frogs, respiration takes place to such an extent through the skin, that the animal will live for a long time after respiratory movements have ceased. Respiration also takes place through the skin in man, but to a very slight extent, the absorption of oxygen and the excretion of carbonic acid being only about 1/200 th part of that in the lungs.

The skin is able to absorb other gases as well as oxygen, such as sulphuretted hydrogen, carbonic acid, carbonic oxide, and the vapours of hydrocyanic acid, ether, and chloroform.

From the relief which persons who have been shipwrecked and have suffered from extreme thirst have received by bathing in sea-water, or putting on shirts wet with sea-water, it seems probable that the skin is able to absorb water, but this fact also shows that solids dissolved in the water are not absorbed by the skin. A good deal of discussion has taken place regarding the absorption by the skin of substances applied to it in a state of solution. Experiments on this point have usually been made with iodide of potassium, on account of the ease with which this salt can be detected in the urine. The results have generally been negative, but sometimes they have been positive. The general result is that the salt is never absorbed by the skin from the solution, and that in the cases where absorption has taken place, it has been due to the skin not having been washed after the bath, so that the iodide has crystallised on the surface, and has afterwards by friction of the clothes been rubbed into the sebaceous glands. It would appear that the fat in the skin as well as the epidermis presents an obstacle to the absorption of substances in solution, but when they are applied in such a form that they can readily mix with the sebaceous matter of the skin, they are tolerably readily absorbed, as for example when they are used in the form of ointment and well rubbed into the skin, so as to penetrate into the sebaceous follicles and also the sweat-glands. They are also absorbed when dissolved in ether, and especially in chloroform, even when simply painted over the surface. Alcoholic solutions are not absorbed when painted on in this way, although they may be absorbed if rubbed well in. It has been supposed that the absorption of chloroform solution is due to the chloroform mixing with the sebaceous matter. But, if true at all, this is certainly not the complete explanation of the fact, for as has just been mentioned, alcoholic solutions are not absorbed, although alcohol as well as chloroform will dissolve sebaceous matter. Waller has also shown that chloroform passes rapidly through the dead skin, carrying with it alkaloids dissolved in it. Its action is therefore to a great extent due to its peculiar endos-motic power.

The vascularity of the skin greatly alters its absorptive power.. In the frog, absorption usually occurs rapidly through the skin, so that if the hind legs be immersed for a few minutes in a solution of cyanide of potassium, the salt is rapidly absorbed and can be detected in the mouth of the animal in a few minutes. But if the circulation be depressed by the previous administration of ether, curare, or any cardiac depressant, this absorption into the system does not take place; for although the cyanide of potassium passes through the skin, yet, the subcutaneous circulation being feeble, it is not conveyed away from the point of local application into the system generally.

The absorption of drugs may therefore be diminished by depression of the circulation either locally at the point of application or in the system generally. It may be rendered more rapid by increased circulation at the point of application. A general increase in the circulation usually accelerates the circulation in the different parts of the body, but does not necessarily do so, for the vessels of a part may remain contracted while the general circulation is more rapid than usual.

A local increase in the circulation occurs from inflammation of a part, or from temporary irritation such as that produced by rubbing, or by the application of irritant substances. The use of friction, therefore, increases absorption not only by pressing the substances employed into the sweat-glands and hair-follicles but also by increasing the circulation, and this effect will take place to a still greater extent if the substances used have a tendency to cause dilatation of the vessels.

The most common methods of applying drugs epidermically are baths, poultices, inunction, and friction.