8. The last modifying cause to be mentioned comprehends certain

_diseased states of the body_. The effect of disease, like that of habit, is in general to impair the activity of poisons. But it is only in the instance of a few diseases that this diminution is so strongly marked as to be important in relation to medical jurisprudence.—In the continued fever of this country there is a diminished susceptibility of the constitutional action of mercury; and this peculiarity is very strongly marked in the yellow fever, as well as in the bilious fevers generally of tropical climates. In some varieties of typhoid fever there is obviously a diminished sensibility to the action of wine and other spirituous liquors; but this diminution in a great majority of cases is much inferior to what some physicians have represented.—In severe dysentery the susceptibility of the narcotic action of opium is so much impaired, that a person unaccustomed to the use of that drug, may continue to take daily, for several days together, a quantity which might prove fatal to him in a state of health. In the severe form which dysentery occasionally puts on in this country I have known a patient take from twenty-four to thirty grains of opium daily, and retain it all, without experiencing more than a mild narcotic action.—In epidemic cholera the same insensibility has been remarked to the operation of opium.—It also occurs in the instance of excessive hemorrhagy.—According to the doctrines and practice of the present dominant school in Italy, there is an unusual insensibility during inflammatory dropsy to the irritant action of gamboge, so that sixty or eighty grains may be taken without harm.—There is no disease, however, in which the power of mitigating the action of poisons is more remarkably exhibited, than in tetanus: It is often scarcely possible to bring on the narcotic action of opium by any doses which can be administered; calomel, too, acts with much less energy than usual; and even common purgatives must be administered in doses considerably larger than those required in most other disorders.—Mania is similarly circumstanced: almost all remedies must be given in increased doses, narcotic remedies in particular. But there is good reason for believing that the impaired susceptibility of the action of poisons remarked in this disorder is far from being always so great as some have alleged.—Another disease allied to the last, where the diminution of susceptibility is often great, is delirium tremens. It has in particular been often found, that to produce sleep in this disease opium must be given in frequent large doses,—so large indeed, that they would undoubtedly prove fatal to a person in health. At the same time it is worthy of remark, that in some cases of delirium tremens, even violent in degree, the peculiarity now specified, as I have myself several times witnessed, is far from being strongly marked.—Hydrophobia always, and hysteria sometimes, impair the activity of poisons. I have seen cases of hysteria, more particularly those assuming the form of tetanus, where very large doses of opium were required to produce a calmative effect and sleep; and in hydrophobia it is well shown that the narcotic action of opium is not produced even by large doses often repeated.—The same state occurs in excessive hemorrhage. In the operation of this class of modifying agents it is a general law, to which there are probably few exceptions, that they chiefly affect poisons of the organic kingdoms, and the narcotics above all. At least in the instance of most mineral poisons their influence is very inferior. Their operation may be accounted for in various ways. Sometimes, as in dysentery and cholera, the poison is carried with unusual rapidity through the alimentary canal. Sometimes again it remains comparatively inert, because on account of the impaired activity of absorption, it is not taken up with the usual quickness by the absorbent vessels. And sometimes, as in the instance of tetanus, mania, and rabies, the nervous system is in a state of peculiar excitement, by which the customary action of the poison is in a great measure, if not entirely, counteracted. In a few diseased states of the system there is an increased susceptibility of the action of poisons: and it is important that the medical jurist should attend to this circumstance. When a poison has a tendency to bring on a peculiar pathological state of the system, or of a particular organ, which state is also produced by a disease existing at the time or impending, violent and even fatal consequences may ensue from doses of poisons which in ordinary circumstances are innocuous or beneficial. Thus in persons affected with apoplexy an ordinary dose of opium may accelerate death; and in people even with a mere tendency to apoplexy, if it is strongly marked, or appears from what are called warning symptoms to be on the point of developing itself, a common dose of such narcotics as occasion determination to the brain may excite the apoplectic attack. Thus, too, in cases of inflammatory disorders of the alimentary canal, irritating substances, in doses not otherwise injurious, may produce dangerous impressions on the tender membrane with which they come in contact. But in respect to this last example, it must be remarked, that the improvements or the caprice of medical practice have gone directly in face of the rule, by suggesting that some internal inflammations of the alimentary canal may be successfully treated with irritating remedies. I might here perhaps have added among the causes which modify the action of poisons, sleep, and the administration of other poisons. The latter subject, however, will be better considered at the end of the Individual Poisons, under the title of Compound Poisoning. The former agent is of doubtful effect. Some observations on its influence will be found in the chapter on the Evidence of General Poisoning, p. 41. _Application of the preceding remarks to the Treatment of Poisoning._ As an appendix to what has been said respecting the physiological action of poisons, and the causes by which it is liable to be modified, I shall here state shortly certain applications to the treatment of poisoning. In the instance of internal poisoning, the great object of the physician is to administer an antidote or counter-poison. Antidotes are of two kinds. One kind takes away the deleterious qualities of the poison before it comes within its sphere of action, by altering its chemical nature. The other controls the poisonous action after it has begun, by exciting a contrary action in the system. In the early ages of medicine almost all antidotes were believed to be of the latter description, but in fact very few antidotes of the kind are known. Chemical antidotes operate in several ways, according to the mode of action of the poison for which they are given. If the poison is a pure corrosive, such as a mineral acid, it will be sufficient that the antidote destroy its corrosive quality: Thus the addition of an alkali or earth will neutralize sulphuric acid, and destroy or at least prodigiously lessen its poisonous properties. In applying this rule care must be taken to choose an antidote which is either inert in itself, or, if poisonous, is, like the poison for which it is given, a pure corrosive or local irritant, and one whose properties are reciprocally neutralized. If the poison, on the other hand, besides possessing a local action, likewise acts remotely through absorption, or by an impression on the inner coat of the vessels, mere neutralization of its chemical properties is not sufficient; for we have seen above that such poisons act throughout all their chemical combinations which are soluble. Here, therefore, it is necessary that the chemical antidote render the poison insoluble or nearly so; and insoluble not only in water, but likewise in the animal fluids, more particularly the juices of the stomach. The same quality is desirable even in the antidotes for the pure corrosives; for it often happens that in their soluble combinations these substances retain some irritating, though not any corrosive power. When we try by the foregoing criterions many of the antidotes which have been proposed for various poisons, they will be found defective; and precise experiments have in recent times actually proved them to be so. The other kind of antidote operates not by altering the form of the poison, but by exciting in the system an action contrary to that established by the poison. On considering attentively, however, the phenomena of the action of individual poisons, it will be found exceedingly difficult to say what is the essence of a contrary action, and still more how that counter-action is to be brought about. Accordingly, few antidotes of the kind are known. Physiology or experience has not yet brought to light any mode of inducing an action counter to that caused by arsenic and most of the irritant class of poisons. It appears probable that the remote operation of lead may be sometimes corrected by mercury given to salivation, and that the violent salivation caused by mercury may be occasionally corrected by nauseating doses of antimony. But these are the only instances which occur to me at present of antidotes for irritant poisoning which operate by counter-action, unless we choose to designate by the name of antidote the conjunction of remedial means which constitute the antiphlogistic method of cure. In the class of narcotics we are acquainted with equally few constitutional antidotes, although the nature of the action of these poisons seems better to admit of them. Ammonia is to a certain extent an antidote for hydrocyanic acid, but by no means so powerful as some persons believe; and I am not sure that in this class of poisons we can with any propriety mention another antidote of the constitutional kind. On the whole, then, it is chiefly among the changes induced by chemical affinities that the practitioner must look for counter-poisons; and the ingenuity of the toxicologists has thence supplied the materia medica with many of singular efficacy. When given in time, magnesia or chalk is an antidote for the mineral acids and oxalic acid, albumen for corrosive sublimate and verdigris, bark for tartar-emetic, common salt for lunar caustic, sulphate of soda or magnesia for sugar of lead and muriate of baryta, chloride of lime or soda for liver of sulphur, vinegar or oil for the fixed alkalis; and these substances act either by neutralizing the corrosive power of the poison, or by forming with it an insoluble compound. In recent times a new object in the treatment of poisoning has been pointed out by the discoveries made in its physiology. As it has been proved that many of the most deadly poisons enter the blood, and in all probability act by circulating with that fluid, so it has been inferred that an important object in the treatment is to promote their discharge by the natural secretions. In support of this reasonable inference it has been lately rendered probable by Orfila, as will be seen under the head of the treatment of the effects of arsenic, that it is of great advantage in some forms of poisoning to increase the discharge of urine. In the instance of external poisoning the main object of the treatment is to prevent the poison from entering the blood, or to remove it from the local vessels which it has entered. One mode, which has been known to the profession from early times, and after being long in disuse was lately revived by Sir D. Barry, and applied with success to man, is the application of cupping-glasses to the part where the poison has been introduced.[60] This method may act in various ways. It certainly prevents the farther absorption of the poison by suspending for a time the absorbing power of the vessels of the part covered by the cup. It also sucks the blood out of the wound, and may consequently wash the poison away with it. Possibly it likewise compresses the nerves around, and prevents the impression made by the poison on their sentient extremities from being transmitted along their filaments. Another mode is by the application of a ligature between the injured part and the trunk, so as to check the circulation. This is a very ancient practice in the case of poisoned wounds, and is known even to savages. But as usually practised it is only a temporary cure: As soon as the ligature is removed the effects of the poison begin. It may be employed, however, for many kinds of poisoning through wounds, so as to effect a radical cure. We have seen that most poisons of the organic kingdom are in no long time either thrown off by the system or decomposed in the blood. Hence if the quantity given has not been too large, recovery will take place. Now, by means of a ligature, which is removed for a short time at moderately distant intervals, a poison, which has been introduced into a wound beyond the reach of extraction, may be gradually admitted into the system in successive quantities, each too small to cause death or serious mischief, and be thus in the end entirely removed and destroyed. Such is a practical application which may be made of some ingenious experiments performed not long ago by M. Bouillaud with strychnia, the poisonous principle of nux-vomica.[61] The last mode to be mentioned is by a combination of the ligature with venesection, deduced by M. Vernière from his experimental researches formerly noticed (p. 19). Suppose a fatal dose of extract of nux-vomica has been thrust into the paw of a dog; M. Vernière applies a tight ligature round the limb, next injects slowly as much warm water into the jugular vein as the animal can safely bear, and then slackens the ligature. The state of venous _plethora_ thus induced completely suspends absorption. The ligature is next tied so as to compress the veins without compressing the arteries of the limb, and a vein is opened between the wound and the ligature in such a situation, that the blood which flows out must previously pass through, or at least near the poisoned wound. When a moderate quantity has been withdrawn, the ligature may be removed with safety; and the extraction of the poison may be farther proved by the blood that has been drawn being injected into the veins of another animal; for rapid death by tetanus will be the result.[62] It is not improbable that in this plan the preliminary production of venous plethora may be dispensed with; and then the treatment may be easily and safely applied to the human subject.