The secondary operation of medicines has been already defined to be that which follows their original and characteristic impression, in consequence of certain physiological laws. Without treating in this place of the resulting effects, it will be proper to explain, in a general way, the several modes in which they are produced.

1. By the Depression following Excitement

It is a general physiological law, that excessive exitement of any function must be followed by a corresponding degree of depression, upon the removal of the cause. When, therefore, an excitant medicine ceases to act, its original and characteristic operation is succeeded not only by a subsidence of the excitement, but by a reduction of the actions of the part affected below the standard of health. This depression is often experienced even before the complete elimination of the medicine from the system; for the excitability may have been so far exhausted by the excess, that the influence of the excitant ceases to be felt, and the healthy vital stimuli have no longer their ordinary influence. The prostration which follows a debauch is often observable, while yet the breath smells of the alcohol.*

2. By the Reaction following Depression

When any of the functions are depressed by an agency which simply restrains action, without impairing the vital forces or deranging the organization, there is a tendency, upon the cessation of the depressing influence, to an elevation of the function beyond its medium state. This depends upon the principle, that excitability is recruited by rest. The resulting elevation of function is usually denominated reaction. It is, however, much less frequently noticed as a consequence of depressing medicines, than the contrary condition of depression after excitants; probably because sedative medicines usually impair power, as well as reduce action. A fine example of it is afforded in the reaction which follows the depressing influence of cold.

3. Through the Dependence of Function

Most of the functions of our system are more or less mutually dependent, so that any considerable derangement of one will in some degree affect the others. A disturbance, therefore, of one of the more influential functions, produced by a medicine acting primarily upon the organs of that function, will be followed by disorder in all the rest; and this disorder will obviously be a secondary effect of the medicine. Thus, alcohol, opium, and quinia, largely taken, occasion so much excitement and active congestion of the nervous centres in the brain, as to disqualify them from transmitting their usual influence to the various organic functions, as those of respiration, circulation, and secretion, which consequently become much depressed; and general prostration ensues. The active cerebral congestion is a primary, the general prostration a secondary effect of the medicine. This is a highly important principle, and of very extensive application. A due attention to it is essential to the practitioner. Suppose that it should be disregarded in the cases just stated, and the prostration considered as the result of the direct and characteristic action of the medicine. A powerful stimulant to the brain might thus be mistaken for a really sedative medicine, and administered with the most serious results in cases of cerebral disease.

In like manner, a medicine, powerfully depressing in its action upon the cerebral centres, would be followed by great general prostration; and this would really be, as well as in the former instance, a secondary effect: but there is not the same necessity for making the distinction; because the secondary is of the same character with the primary effect, and no mistake could occur of the nature of that above referred to.

* This law of depression following excitement is denied by some late writers; and there may be one or two apparent exceptions to the universality of the law, as in the instance of nitrous oxide; but of its general truth I can have no doubt. The point is one not of theory but observation; and every one must be determined by his own experience. Mine has been most assuredly in favour of the existence of such a law. {Note to the third edition).

The results of what is denominated the shock, are another example of the secondary operation of medicines belonging to the same category. Any sudden and violent impression, as from a fall, a blow, a surgical operation, or some strong emotion, primarily overwhelms and paralyzes the cerebral centres, and secondarily occasions general prostration. Now-certain medicines of great violence, as for example the corrosive poisons taken largely into the stomach, may produce a similar shock upon the nervous centres, followed by a similar general depression, which, without a knowledge of this principle, might be mistaken for the result of a directly depressing agency, and treated as such with very serious consequences.

The operation upon the system at large of medicines which act by changing the character of the blood, is another example of the same kind. The general effects result from the state of the blood, and not from the immediate influence of the medicine, and are, therefore, secondary effects of the latter.

4. Through the Principle of Sympathy, or Nervous Transmission

Though it is not probable that special or peculiar impressions of medicines are, to any considerable extent, conveyed from the part impressed through the nerves to the nervous centres, and thence transmitted to other parts, yet mere excitative impressions, or those consisting in pure irritation or inflammation, are undoubtedly thus conveyed. What is special in the influence of the medicine is, therefore, mainly limited to its surface of contact; while it is only the pure irritation, such as may result from any irritating cause whatever, that is conveyed away, and propagated through the nerves. This transmission of irritation arises from a general physiological law, and is, therefore, a secondary effect of the medicine. Thus, a rubefacient or epispastic may excite so much local inflammation as, through the nervous centres, to bring many of the organs into sympathy, and in this way to produce general excitement. and even fever. The increased frequency of pulse, heat of skin, cerebral disturbance, etc., which enter into this excitement, are secondary effects of the rubefacient or epispastic, the primary action of which is limited to the portion of skin to which it was applied. This principle is also of extensive application in explaining the effects of medicine.

5. Through the Principle of Revulsion or Derivation

There is in the system but a limited amount of blood, and of nervous power. When these are concentrated, or accumulated in undue amount, by the influence of a local irritant or otherwise, in some one part or organ, they must be deficient elsewhere; and a depression must ensue in those functions which are not irritated by sympathy with the part or organ originally affected. Supposing the local accumulation of blood and nervous power to be the result of the action of a medicinal agent, the depression produced elsewhere is a secondary effect of that agent. Now it may have happened that the parts depressed were previously in a state of morbid excitement, which has thus been diminished, and perhaps entirely removed by the direction given towards the seat of the primary influence. The name of revulsion or derivation has been given to this forced transfer of morbid action; and we frequently avail ourselves of the principle in the treatment of disease. It is upon this principle that a blister relieves internal inflammation. It is upon this, also, in part, that a cathartic, by producing a moderate irritation along the whole course of the intestine, draws off morbid excitement from other organs, and especially from the brain. Indeed, whatever remedy occasions a local irritation may thus prove the means of unseating irritation elsewhere. It is quite obvious that the diversion of disease, thus effected, is a secondary operation of the remedy.

Upon the same principle exactly, operating reversely, a depression of any part or organ, by diminishing the blood and nervous power in the part affected, must cause their accumulation elsewhere; and thus, depressing or sedative medicines, acting locally, may, through a secondary operation, cause irritation in some other position. For example, cold water applied to a gouty foot, by diminishing the inflammatory excitement there, may secondarily occasion inflammation of the stomach. Medicines are not often employed in reference to such effects; but this mode of secondary action should be understood, if on no other account, at least in order that its injurious effects may be guarded against.

6. Through the Efforts of Nature to Repair Injuries

It may be considered as a general law of the animal economy, that, when any injurious influence is exerted upon the system, actions are induced with the object, and frequently with the effect, of obviating the injury, or repairing the damage inflicted. It is probable that many diseases are nothing more than the struggles of the system to free itself from some noxious agent, or to counteract its influence. The abnormal impressions made by medicines are often, no doubt, upon this principle, followed by resisting or corrective efforts of nature, which must rank among the secondary effects of the medicine, and may sometimes be taken advantage of for remedial purposes. Thus, the death of a part produced by an escharotic is the primary effect of the medicine; the subsequent inflammation, ulceration, sloughing, and suppurative discharge, are secondary effects, intended for the repair of the injury, and useful in reference to pre-existing disease, upon the principles of revulsion and depletion.

7. Through the Removal of the Cause

Very many of the morbid actions or states of the system are secondary, depending upon the existence of some other action or condition, upon the removal of which the effect also ceases. It is obvious that a medicine, which by its primary operation removes the cause, and thus cures the disease, acts secondarily in relation to the latter effect. Thus, acid in the stomach often occasions severe headache, which is cured by an antacid, or an emetic. The neutralization or evacuation of the offending agent is the primary operation of the medicine, the cessation of the headache a secondarv effect. This is a very extensive remedial principle.

It is very often difficult to determine which are primary and which secondary effects of medicines; and the decision of the question will often rest on the view which may be entertained of the mode of action of the remedy. In the instance, for example, of a sedative depressing the cerebral functions, the question of its primary or secondary action on the brain will be determined by our opinion upon the point, whether it is merely carried by the blood to the brain, or operates on that organ exclusively through changes first produced in the blood, incapacitating that fluid for the performance of its proper functions. In the latter case, the characteristic sedative operation of the medicine must be considered as secondary. But it is the safest rule to consider the obvious effects of a remedy as primary, unless some intermediate stage in its operation can be positively demonstrated, or rendered extremely probable by observed facts.