Drug-Induced Gallbladder Disease

Abstract

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 hypersecretion 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 hypersensitivity-induced cholecystitis. Furthermore, there are reports on the influence of cyclosporin, dapsone, anticoagulant treatment, and narcotic and anticholinergic medication in causing gallbladder disease.

Prevalence of Symptomatic Gallbladder Disease After Bariatric Surgery: A Literature Review

“…Furthermore, the risk of GBD development may be heightened by using certain medications, which can impact the disease through several theoretical mechanisms. Some medications may affect lipoprotein uptake by hepatocytes or inhibit the activity of acyl coenzyme A-cholesterol acyltransferase, leading to bile production with sludge [ 5 , 14 , 15 ]. Other medications may promote the precipitation of bile salt formations, while less common mechanisms include hypersensitivity cholecystitis [ 5 , 14 , 15 ].…”

“…Some medications may affect lipoprotein uptake by hepatocytes or inhibit the activity of acyl coenzyme A-cholesterol acyltransferase, leading to bile production with sludge [ 5 , 14 , 15 ]. Other medications may promote the precipitation of bile salt formations, while less common mechanisms include hypersensitivity cholecystitis [ 5 , 14 , 15 ].…”

Demographic, Chemical, and Helicobacter pylori Positivity Assessment in Different Types of Gallstones and the Bile in a Random Sample of Cholecystectomied Iranian Patients with Cholelithiasis

“…Some drugs are reported to make gallbladder stones by different pathogenetic mechanisms, such as estrogens, progesterone, oral contraceptives, clofibrate, ceftriaxone, octreotide, erythromycin, ampicillin, thiazide diuretics, somatostatin analogs, cyclosporin, dapsone, anticoagulant treatment, and narcotic and anticholinergic medications [ 29 , 30 ]. In our study, PPI was the most common drug used.…”

Daclatasvir and Asunaprevir Combination Therapy-induced Hepatitis and Cholecystitis with Coagulation Disorder due to Hypersensitivity Reactions

“…We diagnosed the patients with acalculous cholecystitis based on the findings from the physical examination, such as tenderness in the right hypochondrium; the laboratory data, such as an increase in the WBC count and elevation of CRP levels; and the imaging findings, such as wall thickening and debris in the gallbladder. A number of drugs have been reported to induce gallbladder diseases, including hypersensitivity-induced cholecystitis ( 13 ). Most cases of acute cholecystitis are caused by gallstones, but an allergic reaction has also been reported to be involved in some cases ( 14 ).…”