Stomach

Through its central action it tends to lessen motor activity and to retard the secretion of gastric juice. Riegel, also Hirsch, asserts that after a temporary diminution the secretion increases to beyond the normal. The motor functions are decidedly retarded. Hirsch noted a tonic spasm of the pyloric sphincter, and this was confirmed by the x-ray observations of Magnus on cats. Instead of two or three hours for the stomach to empty itself, a hypodermic of 1/6 grain (0.01 gm.) made the emptying time eight to twelve or even twenty-four hours, the fundal end of the stomach tending to dilate and lose its tone. In many Roentgen-ray examinations in 12 patients, Pancoast and Hopkins obtained in most instances some pyloric spasm with prolongation of the emptying time, the effect being the same whether the drug was given by mouth or subcutaneously. There was usually hyperperistalsis at the pyloric end of the stomach. Mtiller and Saxl noted dilatation of the fundus, with a doubling of the capacity of the stomach. Rarely an hourglass contraction occurs. Morphine may thus be a cause of acute dilatation of the stomach.

Our chief concern as regards the stomach is the undesirable after-effect of nausea and vomiting. To what these are due is not positively known. A dog regularly vomits a few minutes after a dose of morphine - even a minute dose, as 0.0001 gm. per kilo - whether given by mouth or hypodermatically; but in man there is no nausea for several hours. Hatcher says that dogs do not vomit if the morphine is preceded by atropine. That the effects are not due, at least in man, to excretion of morphine itself is indicated by the fact that doses administered by mouth have no especially nauseating effect before absorption, and by Alt's finding that after a hypodermic injection morphine appeared in the saliva in two and one-half minutes, and in the gastric secretion in three minutes, and had disappeared from the stomach in an hour - long before the nausea developed. It would seem to be due, therefore, in man, to the formation from the morphine -of some substance with an apomorphine effect upon the vomiting center. In spite of this nauseating tendency, morphine, because of its central sedative action, will prevent the production of vomiting by irritants in the stomach.

Intestines

Morphine diminishes both secretion and peristalsis, but particularly the latter; and so powerful is it that it is regularly employed in peritonitis, or after operations where it is essential to keep the intestines quiet. Because of this ability to keep the bowel immovable it is sometimes called the "bowel splint." It acts when the intestine is severed from the central nervous system, and apparently by depressing the nerve centers in the intestinal walls (Auerbach's plexus). After morphine even local irritants of the intestines do not induce peristalsis. This morphine constipation is often very undesirable and a great drawback to the use of morphine. A factor which perhaps contributes to the constipation is the stomach retention, which not only causes delay in the passage of food, but permits such increased digestion as to lessen the food residue, which is a normal intestinal stimulant. Some observers report a tendency to accumulation in the lower ileum and assume that this is caused by a closure of the ileocolic valve similar to that of the pylorus; but Pancoast and Hopkins find decreased motility throughout the small intestine, especially in the upper part of the jejunum. All investigators agree that there is little if any effect on the colon.

Large doses of opium occasionally result in diarrhea, and this effect may be due to muscle stimulation by members of the phen-anthrene group. Sometimes in painful chronic disease requiring much morphine a long-standing constipation will suddenly change to an intractable diarrhea, and this may be a terminal condition, death following in three or four days. In some cases, too, where constipation results from colicky spasms, a dose of morphine, by allaying irritation and allowing peristalsis to go on, may cause the bowels to move. In colic or pain due to an irremovable source of irritation, e. g., adhesions, morphine may be required to allay the pain; but it should never be employed until all doubt as to the immediate necessity of surgical interference is settled. Many deaths have resulted owing to the postponement of operation, because of the masking of the symptoms by morphine.

Absorption

Morphine is absorbed very rapidly through mucous membranes, and slowly, if at all, through the unbroken skin. When opium is used, the extractive matters retard the absorption of the alkaloids.

Circulation

The direct effect upon heart and arteries is practically none. Sollmann says there is slight stimulation of cardiac muscle, and Macht reports slight dilatation of the coronary arteries. But there is stimulation of the vasoconstrictor center and an important stimulation of the vagus center, the heart, after a large dose, being slowed even to the extent of 10 or 20 beats per minute without change in arterial pressure. An element in the slowing may also be the quiet induced. Hering reports heart-block and auricular fibrillation; the author has seen 2 cases of heart-block. In addition, the cutaneous arterioles may be dilated, with flushing of the skin. In poisoning by morphine the heart frequently remains strong until near death, so that more vigorous restorative measures may be adopted than in poisoning by other narcotics.

Respiration

In the use of morphine in severe diseases the depression of the respiration is a serious drawback. A resting rabbit, expiring 200 c.c. of air in thirty seconds, was given 1/6 grain (0.01 gm.) of morphine (a heavy dose), and the air expired fell to 90 c.c. in the same time. Though the individual respirations were deeper, the breathing was greatly slowed. In poisoning in man the respiration becomes very slow - even down to three or four per minute - the individual inspirations being deep at first but eventually shallow. The breathing is not infrequently of the Cheyne-Stokes type. Macht says that there may be an unmistakable effect on breathing from less than narcotic doses. Cushny and Lieb find that the action is on the intrinsic rhythm of the respiratory center, and that the rate of respiration is decreased independently of the depth.