piperidines and Cholelithiasis

Dyspepsia affects one in four Australians; of those who present in general practice, the majority will have functional or non-ulcer dyspepsia, with no structural explanation for their symptoms. Older patients who present for the first time with dyspepsia, and those with 'alarm features' deserve immediate investigation (preferably by upper endoscopy), to exclude cancer, peptic ulcer or oesophagitis. Other patients may be given empiric therapy (for example, a prokinetic or H2 blocker) initially, but require investigation if this fails. The role of Helicobacter pylori infection in functional dyspepsia is uncertain.

Topics: Adult; Aged; Antacids; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Bismuth; Child; Cholelithiasis; Chronic Disease; Cisapride; Diagnosis, Differential; Domperidone; Dopamine Antagonists; Dyspepsia; Gastroesophageal Reflux; Helicobacter Infections; Helicobacter pylori; Histamine H2 Antagonists; Humans; Metoclopramide; Peptic Ulcer; Piperidines; Stomach Neoplasms

Cholelithiasis affects 10-15% of the adult population in Western society, and about 75% of gallstones are of cholesterol type. Hepatic hypersecretion of cholesterol with the formation of instable cholesterol-rich vesicles in bile, an imbalance between nucleation-inhibiting and nucleation-promoting proteins with further aggregation of cholesterol crystals in a gallbladder with a motility defect (stasis), all play a role in the pathogenesis of cholesterol gallstones. Experimental animal models suggest that gallstone formation can be prevented by improving gallbladder emptying. Thus, a better understanding of the causes underlying the impaired gallbladder motor function in patients with gallstones might lead to the selection of therapeutic approaches for those individuals who are at increased risk for the formation or recurrence of gallstones. The present article focuses on current concepts and theories on the pathogenesis of cholesterol gallstones with emphasis on the gallbladder motility defect. Several treatment strategies for the correction of gallbladder hypomotility are also discussed.

Topics: Adult; Animals; Anti-Bacterial Agents; Cholelithiasis; Cholesterol; Cisapride; Crystallization; Female; Gallbladder Emptying; Humans; Incidence; Macrolides; Male; Parasympathomimetics; Piperidines; Prognosis; Recurrence; Risk Factors

Altered gallbladder motility is regarded as one of the important factors involved in the formation and recurrence of gallstones. Previous studies have suggested that cisapride increases postprandial gallbladder contraction and may therefore be theoretically useful in preventing stone recurrence. The aim of our study was therefore to investigate the effect of cisapride on gallbladder motility in stone-free patients after extracorporeal shock-wave lithotripsy, as compared to healthy volunteers pair-matched for age and sex.. Each subject received cisapride or placebo in a double-blind, cross-over, random order. Gallbladder volumes were measured by ultrasonography in the fasting state and after intake of a standard liquid meal. Plasma cholecystokinin levels were determined by radioimmunoassay.. Fasting gallbladder volumes were smaller in patients as compared to volunteers (20.7 +/- 1.3 ml vs. 46.0 +/- 9.2 ml; p < 0.05) but were not modified by cisapride (21.1 +/- 1.7 ml vs. 58.6 +/- 11.3 ml). The maximal postprandial decrease in gallbladder volume was similar in patients and volunteers (64.5 +/- 12% vs. 62 +/- 10%; NS) and was not significantly altered by cisapride (59 +/- 9.4% vs. 54 +/- 9%; NS). In patients, cisapride increased integrated postprandial gallbladder volume by accelerating gallbladder refilling as compared to placebo by 37 +/- 15% (p < 0.05). Integrated cholecystokinin plasma levels were similar in patients and volunteers and were 13.4 +/- 4.7% higher after cisapride as compared to placebo (p < 0.05).. The results of this study suggest that cisapride does not alter postprandial gallbladder contraction but accelerates gallbladder refilling in patients free from gallstones after extracorporeal shock-wave lithotripsy. This effect of cisapride is probably due to an acceleration of gastric emptying also causing a secondary enhanced cholecystokinin release.

Topics: Adult; Aged; Cholecystokinin; Cholelithiasis; Cisapride; Cross-Over Studies; Double-Blind Method; Female; Gallbladder; Humans; Lithotripsy; Middle Aged; Piperidines; Radioimmunoassay

Stone fragments remaining in the gallbladder are an important problem after ESWL. Cisapride (CIS) improves gallbladder contraction and hence we decided to investigate whether clearance of stone fragments after ESWL for radiolucent gallbladder stones can be increased by cisapride. Six to 15 months (median 12) after ESWL 48 patients with remaining gallstone fragments of less than 5 mm in diameter were randomized either to Group A, who received cisapride 10 mg t.i.d. orally for 3 months in addition to oral litholysis (OLL) with ursodeoxycholic acid 500 mg/day and chenodeoxycholic acid 500 mg/day, or to Group B, who continued solely with OLL. All patients had started OLL within the fortnight-preceding ESWL. Gallbladder contractility, as measured by oral cholecystography with a fatty meal, was intact in all patients prior to ESWL. Maximal diameter and number of fragments were assessed by ultrasound (5 mHz) in different positions of the patient at the beginning of the study and after 3 months. Total clearance of fragments, which includes clearance of all sludge, occurred in only 3 patients, two of whom received only OLL. After 3 months the number of fragments decreased in 6 patients in Group A and in 7 patients in Group B. Three patients stopped taking cisapride before completion of the study, two because of diarrhoea, and one because of dysuria. All symptoms were readily reversible after discontinuing cisapride. In conclusion, cisapride combined with OLL does not enhance clearance of the gallbladder when fragments are still present one year after ESWL.

Topics: Administration, Oral; Adult; Anti-Ulcer Agents; Chenodeoxycholic Acid; Cholelithiasis; Cisapride; Combined Modality Therapy; Female; Follow-Up Studies; Humans; Lithotripsy; Male; Piperidines; Ultrasonography; Ursodeoxycholic Acid

Topics: Adult; Androstanols; Anesthesia, Intravenous; Cholecystectomy, Laparoscopic; Cholelithiasis; Contraindications; Diabetes Mellitus, Type 2; Fentanyl; Humans; Intraoperative Complications; Male; MELAS Syndrome; Neuromuscular Nondepolarizing Agents; Oxygen; Piperidines; Postoperative Complications; Preanesthetic Medication; Preoperative Care; Propofol; Remifentanil; Rocuronium; Succinylcholine

A 54-year-old woman, complicated with myotonic dystrophy, underwent laparoscopic cholecystectomy for cholelithiasis. The patient was given total intravenous anesthesia using propofol, remifentanil and vecuronium, combined with epidural anesthesia using ropivacaine. No complication occurred, and the patient recovered from anesthesia without delay. For the relief of postoperative pain, ropivacaine (0.2%) was given epidurally. The postoperative course was uneventful. The anesthesia with remifentanil is extremely useful for patients with myotonic dystrophy.

Topics: Anesthesia, Epidural; Anesthesia, Intravenous; Cholecystectomy, Laparoscopic; Cholelithiasis; Female; Humans; Middle Aged; Myotonic Dystrophy; Piperidines; Propofol; Remifentanil

We have previously shown that oral cisapride causes a dose-related increase of fasting gallbladder volume in healthy subjects. The present study investigates the effect of cisapride on gallbladder motility in 16 patients with gallbladder stones; 8 patients had no biliary symptoms, but the other 8 patients with symptomatic gallstone disease were studied before and 6 weeks after extracorporeal shock wave lithotripsy (ESWL). For each study the patients received a single oral dose of 20 mg cisapride; fasting gallbladder volume was measured by ultrasound before, and for 120 minutes after, drug administration. In the 8 asymptomatic patients a mean maximal increase of the fasting volume to 152.7 +/- 7.6% of the initial value was observed at a mean 97.5 +/- 8.3 minutes after cisapride ingestion. Similarly, in the 8 patients with biliary pain mean fasting volume after cisapride ingestion increased to 141.3 +/- 5.7% before ESWL treatment and to 145.0 +/- 5.8% after ESWL and 6 weeks of oral litholytic therapy. There were no significant differences between the results in the symptomatic and asymptomatic patients. Our results indicate that cisapride increases the gallbladder volume in gallstone patients regardless of biliary symptoms. Similar volume changes were observed before therapy and after ESWL with bile acid therapy. The therapeutic efficacy of litholytic agents could be diminished by simultaneous cisapride administration.

Topics: Administration, Oral; Adult; Aged; Cholelithiasis; Cisapride; Female; Gallbladder; Humans; Lithotripsy; Male; Middle Aged; Piperidines; Ultrasonography

The hepatic secretion of supersaturated bile and gallbladder stasis are key events in cholesterol gallstone formation. The therapeutic value of cisapride, a prokinetic agent, was assessed in ground squirrels on a 1% cholesterol diet.. Biliary lipid secretion was measured directly and bile salt pool size assessed by isotope dilution ([14C]cholic acid). Gallbladder contraction was measured in vitro in response to cholecystokinin (CCK).. Cholesterol-fed animals had a combined hepatic secretory defect (a 53% decrease in bile salt secretion and also a 31% increase in cholesterol secretion). Adding cisapride restored bile salt secretion to control levels but did not affect cholesterol secretion. In cholesterol-fed animals, the cholesterol saturation index of gallbladder bile more than doubled and cholesterol crystals developed; cisapride markedly reduced cholesterol saturation, thus preventing crystal formation. Gallbladder contractility, measured in vitro in response to CCK, decreased 23% in animals on the 1% cholesterol diet; cisapride restored the CCK dose-response curve to normal. The bile salt pool as assessed by isotope dilution was similar in all groups.. Thus, lithogenic bile develops in this model because of reduced bile salt secretion and increased cholesterol secretion. Cisapride renders biliary lipid composition towards normal by enhancing gallbladder (and possibly intestinal) motility and cycling of the bile salt pool, thereby increasing bile salt secretion.

Topics: Animals; Bile; Bile Acids and Salts; Carbon Radioisotopes; Cholecystokinin; Cholelithiasis; Cholesterol, Dietary; Cholic Acids; Cisapride; Disease Models, Animal; Dose-Response Relationship, Drug; Gallbladder; Gallbladder Diseases; Gallbladder Emptying; Lipid Metabolism; Lipids; Male; Piperidines; Sciuridae; Serotonin Antagonists

Topics: Adult; Aged; Bile; Biliary Dyskinesia; Cholelithiasis; Female; Humans; Liver Diseases; Male; Middle Aged; Migraine Disorders; Piperidines

Topics: Analgesics; Benzophenones; Calculi; Cholelithiasis; Colic; Dipyrone; Drug Combinations; Humans; Kidney; Kidney Calculi; Muscle Relaxants, Central; Myocardial Infarction; Piperidines