Читать книгу The Action of Medicines in the System - Frederick William Headland - Страница 14

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This is to say, that the mere contact of a medicine with the stomach is not in general sufficient for the production of its peculiar action. It will be seen that the only apparent exception to this rule consists of agents having a mere local action on the mucous membrane, for which simple contact is all that is required.

Even when acting on any part of the system removed from this mucous surface, as when applied to the skin, it is necessary that the medicine pass away from it to enter the blood or internal fluids. In the great majority of instances it enters the blood directly. But we know that it would be sufficient for its operation if it were to enter through the chyle, or into the serous fluid which exists in the interstices of the tissues throughout the body. For by these it might at length be conducted to distant parts. This is what is meant by internal fluids.

We are not just now concerned with the way in which this passage into the blood and fluids is obtained. It is by the process of absorption. The question of passage by absorption is treated in the second and third propositions. What we have now to decide is, whether a medicine acts by mere contact with the stomach, its influence being propagated to distant parts by means of the nerves; or by passage thence into the system, acting through the medium of the blood and fluids. I affirm that it operates in this latter way; and this is to be proved by four considerations, which we will consider in succession.

A medicine introduced into the system elsewhere acts in the same way as when introduced into the stomach.

This proves at least that contact with the mucous surface is not an essential requisite for the operation of a remedy. We may cause a medicine to be absorbed by the skin, or inject it directly into an opened vein. The result of this latter experiment proves not only that entry into a distant part of the system is sufficient for the action of a medicine, but that it will operate when introduced into the blood. Numberless proofs of this affirmation may be adduced. Tartar Emetic injected into the veins produces vomiting. Croton Oil rubbed on the surface of the abdomen causes purging. Mercurial ointment applied by friction to the skin will produce salivation. Extract of Belladonna applied to the temples causes dilatation of the pupil of the eye; and tincture of Opium dropped on the eyeball causes the pupil to contract. Ammonia inhaled as gas into the lungs will relieve fainting in the same way as when swallowed. The breathing of Prussic acid, causing its vapour to be applied to the pulmonary surface, is sufficient to kill. Prussic acid, dropped in a concentrated state into the eye of a dog, causes speedy death. Solution of Aconitina, applied to the skin, will produce numbness, and tingling of distant parts. Injection of Nux Vomica, or any powerful poison, into the veins, is rapidly followed by symptoms of poisoning, like those which would have followed its introduction into the stomach.[17] Thus contact with the stomach is not necessary, but introduction into the system any where is sufficient. But still, may not the poison in either case act by influencing the nerves? Even when it has entered the blood, it may not travel along in it, but act in a more direct way. So in the second part of the proof we must show that a remedy cannot act by an impression conducted from the surface of the stomach by means of the nerves.

The continuity of nerve is not necessary for the propagation of such effects; but vascular connexion is necessary.

This alone, if established, would be sufficient to prove that a medicine must be introduced into the circulation, in order to act on distant parts. When confined to a surface, it can operate on the remote part only by its contact with the superficial extremities of the nerves. For vascular connexion to be established, it must first enter the vessels. Many experiments have been made which demonstrate that the vessels are the only channel by which medicinal effects can be propagated.

M. Magendie introduced some Woorara poison into the limb of a dog, which was only connected with the trunk by means of quills uniting the divided ends of the main vessels. It rapidly took effect. Having divided all the nerves and lymphatics in the intestine of another dog, he introduced into it some Nux Vomica, beyond the division. It quickly acted, and must again have done so through the vessels. Sir B. Brodie cut all the nerves of the anterior extremity of a rabbit, near the axilla, and then introduced Woorara into the foot. It rapidly acted.[18] Thus we see that vascular connexion is sufficient, and that nervous connexion is not necessary. By other similar trials it is found that vascular connexion is absolutely necessary, for when it is interrupted, the action cannot be propagated along a nerve. If, on introducing poison into an extremity, a cord be tightened round the limb above it so as to intercept the flow of blood, no effect is produced. It takes effect after the ligature is relaxed. Sir B. Brodie introduced Woorara into the leg of a dog, which was connected with the trunk only by means of the principal nerve, carefully dissected out. No effect followed. M. Ehbert found that poison would not act when applied to an amputated limb connected with the trunk by a nerve only. Thus vascular connexion is necessary; whereas continuity of nerve is not necessary, neither is it sufficient by itself.[19] Woorara poison is a substance which acts with great rapidity on the nervous system; and if its action cannot be propagated by means of the nerves, à fortiori would it seem that slower poisons must act through the circulation. But, granting that it has been shown that introduction into the stomach is not necessary for the action of a medicine, and that when in the stomach medicines do not act by influencing the nerves, still it may be objected that the rule cannot possibly be universal. It may be urged that some poisons and medicines, as Hydrocyanic acid and Ammonia, act with such great rapidity, that we can only suppose their influence to be transmitted directly along a nerve-fibre to the nervous centre, because the process of passage in the blood to this distant part would be far too slow. This argument requires us to prove a third thing.

The circulation of the blood is sufficiently quick to account even for the operation of those poisons which act most rapidly by influencing the nerve-centres.

There is no poison whatever which acts so quickly on distant parts that the circulation cannot previously have had time to conduct it to them. By means of an instrument invented by M. Poisseuille, Dr. Blake found that a chemical substance traversed the whole circulation of a dog in nine seconds, and of a horse in twenty seconds.[20] The results of Hering were similar. M. Volkmann, in the tenth chapter of his work on Hæmadynamics, states, as the result of several experiments, that the whole circulation in an adult man occupies exactly 65.76 seconds.

Now a poison that operated by nervous connexion would probably operate directly when it touched the stomach. This is not the case even with Hydrocyanic acid. This, the most sudden of all poisons, before it takes effect, allows sufficient time to elapse for the blood to conduct it to the brain. Blake made an interesting experiment upon it. He placed some on the tongue of a dog, having first fitted a tube into the larynx, so as to prevent the vapour from passing into the lungs. The effect did not commence until sixteen seconds had elapsed, and forty-five were required for its completion. This allowed of time for absorption.

Thus it is proved that poisons act when introduced into the system at any point; that vascular connexion is required for this action; and that the rapidity of the circulation is in all cases quick enough to account for it.

But this last is only a proof of possibility, and does not by itself show that a substance may not nevertheless act through the nerves. And to the experiments on nervous connexion some may object that no conclusions on this point can be drawn from trials made on isolated and exposed nerves. So we may imagine a person to be still incredulous as to the truth of the Proposition, that medicines must pass into the blood before they can act. But a fourth consideration will suffice to bring this probability as close as possible to a certainty.

The great majority of medicines have been detected in the blood, and found in the secretions formed out of it.

Having tried to prove that they must pass into the blood, if we find that they actually do so, we shall establish a stronger case. Isolated observations on this subject have been frequently made. Thus in 1847 Mr. Allen detected Daturia in the urine of a man poisoned by Stramonium. In 1824 M. Runge had discovered in the same way the principles of Henbane and Belladonna. M. Ragsky has lately detected Chloroform in the blood. (Journal für Prakt. Chem. 1849.) Dr. Golding Bird observes that Indigo, when given for Epilepsy, has turned the urine blue; that Logwood also passes into it, and causes it to give a dark precipitate with solutions containing iron; and that during a course of Copaiba or Cubebs, a resin may be precipitated from it on the addition of Nitric Acid. If a medicine cannot be proved to pass into the blood or secretions, we cannot so certainly affirm that it does not act through the nerves. But the experiments of Tiedemann and Gmelin, and since then of Wöhler, have definitively settled this point. The former two have found the great majority of mineral, and many vegetable substances, in the blood of animals to which they had been administered.

Thus, from these four considerations, we are strictly justified in concluding that a medicine must pass from the stomach into the blood before its action can be manifested. This action cannot then be conducted from the surface of the stomach through the agency of the nerves. Some experiments made by Dr. Garrod and others on the action of animal charcoal as an antidote, furnish again an additional confirmation of this fact. He finds that if a sufficient quantity of this absorbing agent be introduced into the stomach before time has been allowed for the passage of a medicine through the mucous membrane, then even such powerful nerve-medicines as Morphia and Strychnia, in very large doses, are prevented from taking effect. Yet before the contact of the charcoal they would have had time to act through the nerves, had they been capable of any such action.

In the fifth Proposition the rule here laid down will have to be further extended. It will be shown that medicines, having already passed into the blood, must travel along in it so far as to reach the part of the system on which they act.

Before concluding this question, a few remarks must be made on a subject which will be again referred to in the discussion of the Fourth Proposition.

The proper and peculiar action of a medicine, by which I mean that action on the system which is immediately recognised as distinct from that of any other agent, cannot be exerted on distant parts from the stomach-surface, but requires the passage of the medicine into the circulation. But can any other action on distant parts be produced by the remedy while in the stomach? This is a different question, and must be answered in the affirmative. Suppose a Cantharides plaster be applied to the surface of the chest in a case of Pericarditis, so as to redden or blister the skin, absorption of the fluid in the pericardium may follow this application. But any other irritant would have done this. It is not the proper or peculiar action of Cantharides, but an operation of the nervous system which follows the local change. Such agents are said to act by Counter-irritation or Revulsion, because it appears that, as a consequence of their action, the attention of the nervous system may be drawn off from a morbid process going on at some other part of the body. But it is only a consequence, and not a direct operation. Such an effect is no more the action of Cantharides than the healthy functions following recovery from sickness can be ascribed to the remedy which has cured the latter.

Now some few medicines have a marked local action on the mucous surface of the stomach and intestines. (Vide Prop. IV.) These, and these only, may, without passing into the blood, produce on distant parts an action of this kind by counter-irritation. Thus the operation of an irritant emetic may be followed by the arrest of some incipient inflammation, e.g. Ophthalmia. This revulsive action, when carried to an extreme, so powerfully impresses the nervous system, that it puts a stop to all other actions, and produces Syncope or Death. This extreme action is called Shock. Powerful corrosive poisons may effect this by a sudden destruction of the mucous surface, operating like a surgical injury. But such actions, not being the proper and characteristic operations of medicines, but rather attributable to a change in the relations of the nervous system, following a local impression, are not to be considered as exceptions to the above rule, that medicines cannot from the surface of the stomach or intestines propagate their influence to remote parts.