Action Of Drugs On The Intestines 182

Fig. 137. - Represents a piece of duodenum, a, after irritation by potassium chloride; b, after irritation by sodium chloride, o indicates the point of irritation, and the arrows the direction in which the intestinal contents normally move from the pylorus towards the anus. (After Floel.)

1 Nothnagel, Virchow's Archiv, Bd. 88, p. 1. 2 Floel, Pfliiger's Archiv, vol. xxxv. p. 160.

The effect of morphine is very remarkable. When the animal, in addition to being anaesthetised by ether only, as in the previous experiment, has a small dose of morphine injected also into the veins, it has a sedative effect, so that sodium salts applied to the intestine produce only a local contraction like potassium salts. But this is only when a certain dose of morphine is employed, about 0.1 to 0.3 gramme of morphine for a rabbit of average size. When the dose was increased from 0.5 to 0.1 gramme of morphine, an exactly contrary effect was produced, and the application of sodium salts, instead of being followed only by local contraction, caused a peristaltic contraction, which was usually very much more energetic than in the normal condition, and not only spread upwards from the point of contact, but downwards towards the large intestine, which it never did under other circumstances.1 The quieting or inhibitory effect of moderate doses of morphine upon the intestine, irritated by sodium salts, appears to be exercised through the splanchnic nerves, inasmuch as when the mesentery, going to one part of the intestine, is divided in an animal that has received a moderate dose of morphine, the application of sodium salts to this part is followed by a peristaltic wave; while, in the other parts of the intestine where the nerves are uninjured, the sodium salt still produces only local contractions.

Fig. 138.   Represents a piece of intestine, a, at the commencement of contraction, after irritation by sodium chloride; b at the end of contraction. o indicates the point of irritation.

Fig. 138. - Represents a piece of intestine, a, at the commencement of contraction, after irritation by sodium chloride; b at the end of contraction. o indicates the point of irritation. (After Floel.)

From these experiments it is evident that moderate doses of morphine produce a very different effect upon the intestine from large ones : and this effect has indeed been long recognised in practice.

Moderate doses of opium have a constipating action and are constantly used to check diarrhoea, but large doses, such as those taken by opium-eaters, really have no constipating effect. Indeed, large doses of opium injected directly into the jugular vein of a dog act as most energetic purgatives, being much more prompt in their action than almost any other drug that we know. Immediately after their injection the whole intestinal tract is thrown into violent action and its contents expelled, after which it again becomes quiet.

Very minute doses also seem to have a purgative action, as well as very large ones, and I have used them with considerable success in many cases of constipation.

Constipation may be due to diminished peristaltic action, or diminished secretion, or to both, and in some cases is associated with accelerated absorption. In all probability it is generally due to a diminution in the peristaltic action. In the normal condition this ought to go on regularly, so that the bowels should be evacuated, on an average, once a day, though in some persons evacuations normally occur two or three times a day, and in others only once in three or four days. In some apparently healthy persons I have observed an interval of as much as two or three weeks. In some persons the normal stimulus of ordinary easily digestible food does not seem to be sufficient to keep the bowels acting, but food which leaves much indigestible residue, such as brown or bran bread, salad, figs, prunes, or tamarinds, will do so. These latter fruits owe their laxative properties partly to the insoluble residue they leave and which acts as a mechanical irritant to the intestine, and partly to the salts and sugar and mild laxative principles they contain. Treacle and gingerbread also have a useful aperient action, and their pleasant taste makes them specially suitable for children. The effect of a somewhat stimulant article of food is greater when taken on an empty stomach, and thus a fig before breakfast will have a much greater laxative effect than one taken after dinner. A glass of cold water also, by stimulating peristalsis, will have a laxative action when taken on an empty stomach at bed-time or on rising in the morning. When these means are insufficient a slightly irritating substance, such as an aloetic pill taken on an empty stomach just before dinner, will aid the stimulating effect of the food which is taken afterwards, and will be sufficient to ensure perfectly regular and normal evacuations which do not in any way incommode the person. In consequence of this many people continue to take such dinner pills regularly for many years together. Others, again, suffer from constipation, but with them small doses of purgative medicine, if they act at all, act violently, and leave the person weak and uncomfortable, while the bowels again become constipated. This condition is found not unfrequently among women, and is accompanied, sometimes at least, with pain or tenderness in one or both ovaries. In such persons, also, contrary to the general rule, walking exercise increases instead of diminishing constipation.

1 Nothnagel, Virchow's Archiv, Bd. 89, p. 1.

My friend Dr. Litteljohn noticed that in a case of ovarian tenderness, half a grain of opium given to relieve the pain acted as a purgative. On thinking over this, it occurred to me that the constipation in such cases might be due to reflex irritation of the inhibitory intestinal nerves by the tender ovary. It seemed therefore probable that by using graduated doses of opium, one might be able to lessen the action of the inhibitory nerves, or even to divert the stimulus from them on to the stimulating fibres, and thus produce purgation instead of constipation. Not knowing what dose would be sufficient to produce this effect, I began with one drop of tincture of opium given in a teaspoonful of water every night. To my astonishment this dose was not only in most cases sufficient, but in one case it proved excessive, doing no good, while half a drop acted as a brisk purgative. It is evident that opium used in this way will not act as a purgative in cases of constipation depending upon general insensibility of the intestinal nerves. The cases in which it is most useful are those of delicate women of a nervous temperament, suffering from ovarian pain, and in whom, ordinarily, purgatives produce excessive action followed by constipation. Small doses of belladonna have also been recommended in constipation, and it is probable that they act in a similar manner when given alone, and that belladonna, hyoscyamus, and essential oils assist the action of purgatives by tending to divert the stimulus, which the irritating constituent of a purgative produces, from the inhibitory to the accelerating intestinal nerves. We know at present but little regarding diminished secretion as a cause of constipation.

Fig. 139.   Diagram to show the way in which ovarian irritation probably causes constipation.

Fig. 139. - Diagram to show the way in which ovarian irritation probably causes constipation.