Elimination. - Morphine is eliminated by the gastric mucous membrane (p. 39), and may be found in the stomach after subcutaneous injection. It is excreted also in the bile, but may remain a long time in the liver. It is found unchanged in the urine. In cases where its use has been continued for some time, some of it probably becomes changed in the body, as a substance with the chemical reactions of oxydimorphine has been found in the liver and kidneys in such cases (p. 35).

Circumstances Modifying the Action of Opium.

Age. - In childhood the brain is proportionately larger than in adult life and absorption much more rapid, hence the effect of opium is greater than in adults, and children bear it very badly; consequently smaller doses must be given than are proportionate to their ages. Care is necessary from the age of six months to one year, as 1 minim has produced fatal results. In old age the dose must be diminished according to the advance in years.

Sex. - Women are more readily affected than men, and men more liable to nausea and headache after its administration.

Idiosyncrasy. - Small doses easily affect some subjects, and on the other hand large doses are nearly inert in others. Excitement and delirium, instead of quietness and sleep, are not unfrequently produced. In such cases it is best to give a few whiffs of chloroform to quiet the patient and induce sleep, if the excitement has already come on.1 If it is necessary to give opium or morphine to a patient having this idiosyncrasy, it ought to be combined with chloral or a bromide, or with both.

1 Morrant Baker, St. Bartholomew's Hospital Reports.

In some persons excitement and wakefulness occur on the night immediately succeeding the dose, and sleep only occurs on the second night.

Habit. - The effect of habit is perceived in two ways - in some cases large quantities are required to produce a result; in others a long interval is necessary for the drug to take effect. As much as two pints of the tincture have been taken in the course of a day; and as much as 12 grains of morphine have been subcutaneously injected. Both slowness and weakness of action may result from its continued use, so that it may be necessary not only to give a larger dose but to give it a considerable time beforehand. In one case with which I am acquainted, after a few months during which the time gradually increased, it became necessary to give the dose twenty-four hours before its effect was desired.

The explanation of this tardy action probably is that the absorptive power of the intestines is diminished by the continual use of the drug, for it is well known that opium-eaters can take large doses of corrosive sublimate without experiencing any ill-effects, the drug being but slowly absorbed.

But it is quite possible, indeed probable, that there is, besides delayed absorption, another factor in the tolerance of opium induced by repeated doses. It is possible that part of the morphine introduced is converted in the organism into oxydimor-phine, which appears, to a certain extent, to counteract the soporific action of morphine,1 or into other substances which may have this action (see p. 35). Each dose of morphine will thus leave in the body substances having an action antagonistic to the next dose, unless a sufficient interval should elapse between them to allow them to be completely eliminated.

Opium-eating - Morphinism. - When opium is first taken, its action is to stimulate and afterwards depress; to remove this depression the individual takes another dose; the habit of taking the drug thus becomes established. The nervous system suffers, the mental powers become enfeebled, the moral faculties perverted, and there is inability to distinguish between truth and falsehood. Then the motor powers are attacked, the gait becomes shuffling and uncertain, and digestion is impaired. The bowels may be constipated, but are generally loose.

When morphine is taken for some time in medicinal doses, obstinate vomiting sometimes sets in and will not yield to ordinary remedies. It is usually checked by discontinuing the administration of the drug. This vomiting may possibly be due to the morphine being converted into oxydimorphine2 or apomorphine in the system.3

1 Diedrich, Ueber Oxydimorphin, Inaug. Diss., Gottingen, 1883.

2 Diedrich, op. cit.

3 The view expressed in the text received a curious confirmation shortly after

If the patient has been accustomed to the use of hypodermic injections of morphine, hypodermic injections of water should be substituted in such cases and the strength supported by careful frequent administration of nourishment.

Disease. - When a patient is suffering intense pain, opium is well borne, and must be given in large quantities; as, for example, to a person suffering from peritonitis. In cases of Bright's disease small doses may produce disproportionately great effects (p. 41). Hence in these cases the drug must not be given in large quantities, and the effect of each dose must be carefully watched.

Combination with other Drugs. - Chloroform sometimes modifies the action of opium, the chloroform narcosis passing into opium sleep, or the opium sleep may more resemble chloroform anaesthesia; hence the use of the two drugs together may be of advantage in certain operations, such as excision of the jaw, where it is difficult to continue administering an anaesthetic (p. 208).

In some cases opium will not produce sleep even in large doses, and it is then advisable to combine it with a small dose of hydrate of chloral. Sometimes when opium has been given to produce sleep, and has only caused excitement, a few whiffs of chloroform will quiet the excitement, and the patient sinks into a quiet sleep.

Action of the Alkaloids of Opium. - The action of the opium alkaloids has not been fully made out, and various results have been obtained by different observers. It is certain, however, that morphine is in mammals almost entirely narcotic, whilst thebaine is purely convulsive. Between these extremes the other alkaloids probably range themselves in such an order that they may be divided into two sub-groups, the first of which may be called the morphine group, characterised by the prominence of the narcotic stage; while in the other, which may be called the codeine group, the tetanic stage is more prominent, and the narcotic less so. The members of these groups may be arranged as follows, so that each subsequent member has a weaker narcotic, and in the codeine group has at the same time a stronger convulsive, action :Morphine Group.