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Oral erythromycin improves gastrointestinal motility and transit after subtotal but not total gastrectomy for cancer.

BACKGROUND: Erythromycin has been shown to be a powerful prokinetic of the gastrointestinal tract. Little is known about its value to improve motility and transit in gastrectomized patients. METHODS: Thirteen disease-free patients subjected to subtotal gastrectomy and 11 subjected to total gastrectomy for gastric cancer entered the study. Gastrointestinal transit of a standard 99mTc-labelled meal and fasting motility were studied before and after oral erythromycin. RESULTS: In patients who had subtotal gastrectomy mean(s.d.) gastric half-emptying time was 42(14) min before and 26(11) min after erythromycin (P = 0.011). Before erythromycin prolonged rhythmical contractions (3 per min) were recorded in eight patients, sporadic non-organized contractions in two and prolonged bursts of waves in one. After erythromycin, clustered waves resembling a migrating motor complex (MMC) appeared in eight patients, while rhythmic motor activity was unchanged in three. In patients who had total gastrectomy jejunal half-emptying time was 39(18) min before and 45(12) min after erythromycin. In eight patients, frequent MMCs were recorded, peristaltic in four, synchronous in one, antiperistaltic in two, with clusters of non-propagated waves in one. After erythromycin, longer peristaltic MMCs were recorded in three, antiperistaltic MMCs persisted in two, synchronous in one and clusters of non-propagated waves in two. CONCLUSION: Oral erythromycin improves gastrointestinal transit and motility after subtotal gastrectomy. The findings after total gastrectomy are controversial.

Administration, Oral↗

Macrolides and gastrointestinal motility.

Erythromycin was the first macrolide used clinically, and it is still the most widely prescribed in spite of reports of gastrointestinal side-effects. Erythromycin was given iv or orally to fasted and fed dogs with sensors implanted on the gastrointestinal tract for the measurement of motility. There was a large increase in stomach and upper small bowel contractile activity, accompanied by nausea and vomiting, while the distal small bowel appeared inhibited. Similar effects were seen in man. By contrast, two 16-membered macrolides, spiramycin and josamycin, did not produce such side-effects when given either orally or intravenously to dogs.

Erythromycin↗

Central administration of Tyr-MIF-1 stimulates gastrointestinal motility in rats: evidence for the involvement of dopamine, sigma and CCK receptors.

The effect of central administration of the endogenous peptide Tyr-MIF-1 (Tyr-Pro-Leu-Gly-NH2) on the gastrointestinal myoelectric activity and its mechanism of action were studied in rats. Tyr-MIF-1 (40 & 80 micrograms/kg i.c.v.) stimulated antral and duodenal myoelectric activity in a multiphasic manner. On the antrum it induced a primary increase of the frequency of antral spike bursts followed by a consecutive return to control value and a second rise of the frequency. Likewise duodenal migrating myoelectric complexes (MMCs) were initially disrupted and replaced by an irregular spiking activity followed by a reaparition of the phase III of the MMCs with increased amplitude and frequency. Haloperidol (1 mg/kg i.p.) blocked all the effects of Tyr-MIF-1 whereas sulpiride (5 mg/kg s.c.) blocked only the duodenal stimulation without affecting that on the antrum. Similarly BMY-14802 (0.5 mg/kg s.c.) antagonized selectively the primary antral stimulation and the initial disruption of duodenal MMC induced by Tyr-MIF-1. L365 260 (10 micrograms/kg i.c.v.) has also antagonized only the initial disruption of duodenal MMCs. DTG and JO 1784 (100 micrograms/kg i.c.v. each) reproduced fully the effect of Tyr-MIF-1 on the duodenum but not that on the antrum. Domperidone, (+)SCH 23390, devazepide, PK 11-195 and flumazenil did not have effect on the action of Tyr-MIF-1. It is concluded that Tyr-MIF-1 stimulates the antrum involving haloperidol sensitive but nondopamine, dopamine, probably sigma receptors, and the duodenum via a pathway where central D2 dopamine, sigma and CCKB receptors are implied.

Action Potentials↗

A novel 5-HT3 receptor agonist, YM-31636, increases gastrointestinal motility without increasing abdominal pain.

We examined the effects of YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate), a novel 5-HT3 receptor agonist, on gastrointestinal functions including visceral pain reflex in rats. Injection of YM-31636 increased the number of fecal pellets. This effect was completely inhibited by ramosetron, a 5-HT3 receptor antagonist. YM-31636 also increased the intracolonic pressure measured in both conscious and anesthetized rats. In isolated distal colon, YM-31636 increased the short-circuit current response. This effect was abolished by ramosetron. Both the maximal response and the potency of YM-31636 were weaker than those of other 5-HT3 receptor agonists. In two visceral pain reflex models, YM-31636 neither changed the magnitude of pressor response to colonic distension in anesthetized rats nor affected the visceromotor threshold to colorectal distension in conscious rats. In conclusion, YM-31636 facilitated defecation without increasing visceral pain. Consequently, 5-HT3 receptor agonists like YM-31636 would be promising in the treatment of chronic constipation.

Abdominal Pain↗

Gastrointestinal motility in normal subjects and patients with diverticulosis of the colon.

Our study included 25 subjects, ten with normal intestinal habits and 15 with colonic diverticulosis. Data was collected from X-rays of gastrointestinal transit times and from intraluminal pressures in the sigmoid and rectum, using electromanometry. A comparison of the results led to the following conclusions: 1) transit times to the cecum were essentially similar in both the control subjects and patients with diverticulosis; 2) the barium contrast arrived twice as fast in the proximal sigmoid of patients with diverticulosis compared to the control group. Therefore, there is an increase in the transit between the cecum and sigmoid in individuals with diverticulosis of the colon; 3) the mean of the total time of gastrointestinal emptying is similar in both groups; 4) under unstimulated conditions, the electromanometric study of the sigmoid and rectum was similar in both groups; 5) the sigmoid region in patients with diverticulosis has a modulating transit capacity delaying it. This modulation was not reflected in the electromanometric study as an increase in motor activity.

Adult↗