Drug-Induced Gallbladder Disease
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A great variety of drugs is reported to induce gallbladder disease by various pathogenetic mechanisms.
Early epidemiological studies indicated a doubled risk of gallbladder disease in women taking oral contraceptives. More recent studies, however, have failed to confirm those findings; these conflicting results might be explained by the different methods used to define gallbladder disease. It was shown that the lithogenic index of the bile is increased during intake of oral contraceptives. Estrogens cause hypersécrétion of cholesterol in bile, due to increase in lipoprotein uptake by the hepatocyte. Progesterone inhibits acyl coenzyme A-cholesterol acyl transferase (ACAT) activity, causing delayed conversion of cholesterol to cholesterol esters.
Of the lipid lowering drugs, only clofibrate has been shown to increase the risk for gallstone formation. The other fibric acid derivatives have similar properties, but clinical experience is not as extensive. They seem to be inhibitors of the ACAT enzyme system, thereby rendering bile more lithogenic.
Conflicting epidemiological data exist regarding the induction of acute cholecystitis by thiazide diuretics.
Ceftriaxone, a third-generation cephalosporin, is reported to induce biliary sludge in 25 to 45% of patients, an effect which is reversible after discontinuing the drug. The sludge is occasionally a clinical problem. It was clearly demonstrated that this sludge is caused by precipitation of the calcium salt of ceftriaxone excreted in the bile.
Long term use of octreotide is complicated by gallstone formation in approximately 50% of patients after 1 year of therapy, due to gallbladder stasis.
Hepatic artery infusion chemotherapy by implanted pump is shown to be associated with a very high risk of chemically induced cholecystitis. Prophylactic cholecystectomy at the time of pump implantation is therefore advocated.
Some drugs, such as erythromcyin or ampicillin, are reported to cause hypersensitivityinduced cholecystitis.
Furthermore, there are reports on the influence of cyclosporin, dapsone, anticoagulant treatment, and narcotic and anticholinergic medication in causing gallbladder disease.
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- Boden G, Shimoyama R. Somatostatinoma. In Cohen & Soloway (Eds) Hormone-producing tumors of the gastrointestinal tract, pp. 85–99, Churchill-Livingstone, New York, 1985Google Scholar
- Boston Collaborative Drug Surveillance Program. Oral contraceptives and venous thromboembolic disease, surgically confirmed gallbladder disease, and breast tumours. Lancet 2: 1399–1404, 1973Google Scholar
- Buscail I, Tauber JP, Puel-Bosquet C, Escourrou J, Bayard F, et al. Gall stones and treatment with octreotide for acromegaly. British Medical Journal 299: 1162, 1989Google Scholar
- Carey MC. Formation of cholesterol gallstones: the new paradigms. In Paumgartner et al. (Eds) Trends in biie acid research, pp. 258–281, Kluwer, Dordrecht, 1989Google Scholar
- Carey MC. Overview of the pathogenetic events in biliary stone formation. In Tytgat & van Blankenstein (Eds) Current topics in gastroenterology and hepatology, pp. 394–402, Georg Thieme verlag, Stuttgart -New York, 1990Google Scholar
- Carey MC, O’Donovan MA. Gallstone disease: current concepts on the epidemiology, pathogenesis and management. In Petersdorf et al. (Eds) Harrison’s principles of internal medicine, update V, pp. 139–168, McGraw-Hill, New York, 1984Google Scholar
- Carrasco CH, Freeny PC, Chuang VP, Wallace S. Chemical cholecystitis associated with hepatic artery infusion chemotherapy. American Journal of Radiology 141: 703–706, 1983Google Scholar
- Case Records of the Massachusetts General Hospital. Case 12-1973. New England Journal of Medicine 288: 620–626, 1973Google Scholar
- Frick MH, Elo O, Haapa K, Heinonen OP, Heinsalmi P, et al. Helsinki heart study: primary-prevention trial with gemfibrozil in middle-aged men with dislipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. New England Journal of Medicine 317: 1237–1245, 1987PubMedCrossRefGoogle Scholar
- Hartmann G, Micheli H, Mordasini R, Noseda G, Stähelin HB. Editorial. Clofibrat — Nutzen oder Schaden? Schweizerische Medizinische Wochenschrift 109: 1137–1139, 1979Google Scholar
- Hunninghake DB. Clinical trials of lovastatin and simvastatin versus cholestyramine. Atherosclerosis Reviews 18: 133–138, 1988Google Scholar
- Jutrus JA, Longtin JM, Levesque HP. Hyperplastic cholecystoses. American Journal of Roentgenology 83: 795–827, 1960Google Scholar
- Keane PF, Clanachan AS, Scott GW. Influence of age, gender, and progesterone on gallbladder motility in vitro. Surgical Forum 35: 467–468, 1984Google Scholar
- Michels NA. Blood supply and anatomy of the upper abdominal organs, J.B. Lippincott, Philadelphia, 1955Google Scholar
- Michielsen P, Pelckmans P, Van Maercke Y. Oral cholecystography or ultrasonography in the diagnosis of calculous gallbladder disease. Acta Gastroenterologica Belgica 51: 215–222, 1988Google Scholar
- Pertsemlidis D, Panveliwalla D, Kimball A. Effects of clofibrate and of oral contraceptives on biliary lipid composition and bile acid kinetics in man. Abstract A99. Gastroenterology 64: 782, 1973Google Scholar
- Rome Group for the Epidemiology and Prevention of Cholelithiasis (GREPCO). Prevalence of gallstone disease in an Italian adult female population. American Journal of Epidemiology 119: 796–805, 1984Google Scholar
- Royal College of General Practitioners’ Oral Contraception Study. Oral contraceptives and gallbladder disease. Lancet 2: 957–959, 1982Google Scholar
- Schiffman ML, Keith FB, Moore EW. Pathogenesis of ceftriaxone-associated biliary sludge: in vitro studies of calcium-ceftriaxone binding and solubility. Gastroenterology 99: 1772–1778, 1990Google Scholar
- Teelmann K, Scharer K, Udaka K. Experimentelle Toxikologie von Ceftriaxone (Ro 13-9904, Rocephin®): Ceftriaxone ein neues parenterales Cephalosporin. In Grieshaber (Ed.) Proceedings of the Hahnenklee-Symposium, September 1981, pp. 91–111, Editiones Roche, Basel, 1982Google Scholar
- Weedon D. Diseases of the gallbladder. In MacSween et al. (Eds) Pathology of the liver, pp. 454–477, Churchill Livingstone, Edinburgh, London, Melbourne and New York, 1987Google Scholar