Biliary dysfunction

Dicyclomine hydrochloride has one eighth of the neii-rotropic activity of atropine and approximately twice the musculotropic activity of papaverine. This preparation. liN introduced in 1950. has minimized the adverse effects asso. dated with the atropine-type compounds. It is used for its spasmolytic effect on variou.s smtxrth muscle spa.snts. particularly those associated with the GI tract. It is also useful in dysmenorrhea. pylorospa.sm. and biliary dysfunction. 

Biliary dysfunction T Absporption of lipophilic compounds t CSA metabolites in blood ... 

Xenobiotic-induced pancreatitis may be accompanied by gross plasma lipid changes that may result from marked changes of carbohydrate metabolism (see Chapter 9). The observation of the presence of gross macroscopic fecal fat content (steatorrhea) can indicate effects on pancreatic function, biliary dysfunction, or intestinal malabsorption. In longer-term studies, malabsorption of fat-soluble vitamins may be reflected by the clinical condition of vitamin-deficient animals. 

Docetaxel Neutropenia (DLT), hyperlacrimation, fluid retention, nail disorders, myelosuppression Use with caution in liver dysfunction. Do not give if biliary tract is obstructed. Premedicate dexamethasone. 

Curtis LR, Williams WL, Mehendale HM. 1979a. Biliary excretory dysfunction following exposure to photomirex and photomirex-carbon tetrachloride combination. Toxicology 13(2) 77-90. 

Hepatic or severe renal dysfunction, including primary biliary cirrhosis preexisting gallbladder disease hypersensitivity to gemfibrozil. 

Vinblastine is an alkaloid derived from the periwinkle plant Vinca rosea. Its mechanism of action involves inhibition of tubulin polymerization, which disrupts assembly of microtubules, an important part of the cytoskeleton and the mitotic spindle. This inhibitory effect results in mitotic arrest in metaphase, bringing cell division to a halt, which then leads to cell death. Vinblastine and other vinca alkaloids are metabolized by the liver P450 system, and the majority of the drug is excreted in feces via the biliary system. As such, dose modification is required in the setting of liver dysfunction. The main adverse effects are outlined in Table 54-4, and they include nausea and vomiting, bone marrow suppression, and alopecia. This agent is also a potent vesicant, and care must be taken in its administration. It has clinical activity in the treatment of Hodgkin s... 

If more cholesterol enters the bile than can be solubilized by the available bile salts and phosphatidylcholine, cholesterol gallstone disease (cholelithiasis) can occur. This is generally caused by gross malabsorption of bile acids from the intestine, obstruction of the biliary tract, or severe hepatic dysfunction, leading to abnormalities in bile or bile salt production. 

Late adverse effects include hepatic dysfunction, with altered liver function tests and hyperbilirubinemia. After prolonged use of nicotinic acid and nicotinyl alcohol, histological changes, for example parenchymal cell injury, portal fibrosis, cholangitis, cholestasis, biliary casts, and lymphocytic infiltrations around the bile ducts, have occasionally been seen. 

These drugs should be avoided in patients with hepatic or renal dysfunction. There appears to be a modest increase in the risk of cholesterol gallstones, reflecting an increase in the cholesterol content of bile. Therefore, fibrates should be used with caution in patients with biliary tract disease or in those at high risk such as women, obese patients, and Native Americans. 

In the clinical setting, anthracyclines are administered via the intravenous route (Table 55 1). The anthracyclines are metabolized extensively in the liver, with reduction and hydrolysis of the ring substituents. The hydroxylated metabolite is an active species, whereas the aglycone is inactive. Up to 50% of drug is eliminated in the feces via biliary excretion, and for this reason dose reduction is required in the setting of liver dysfunction. Although anthracyclines are usually administered on an every-3-week schedule, alternative schedules of administration such as low-dose weekly or 72-96 hour continuous infusions have been shown to yield equivalent clinical efficacy with reduced overall toxicity. 

Pharmacokinetics Paclitaxel is infused over 3-4 hours. Hepatic metabolism and biliary excretion are responsible for elimination of paclitaxel. Thus dose modification is not required in patients with renal impairment, but doses should be reduced in patients with hepatic dysfunction. 

Dose-independent, drug-induced liver dysfunction (cholestatic jaundice) is not an unusual adverse reaction. Caused by a number of different, commonly used drugs, cholestasis is a hypersensitivity reaction that primarily affects the biliary canaliculi, causing an intrahepatic obstructive jaundice. An alteration in... 

GGT does not nsnally form part of the standard LFTs in most laboratories. It is an enzyme fonnd in hepatocytes and biliary epithelial cells, and also in kidney, pancreas, intestine and prostate. It has a higher sensitivity for indicating a problem of liver origin than alkaline phosphatase, but tends to follow a similar pattern. It is released in all types of liver dysfunction and therefore cannot generally be used to differentiate between types. However, a raised GGT with an isolated raised alkaline phosphatase can be suggestive of cholestasis. GGT levels can be ten to 20 times normal in cholestatic disease. 

Bilirubin Produced from haemoglobin during degradation of erythrocytes. Found in bile 5-21 pmol/L Raised in hepatocyte dysfunction, biliary obstruction and haemolysis... 

Jaundice is also caused by dysfunction in the secretion of bilirubin. The mechanisms involved in the excretion of bilirubin into the biliary capillaries are, however, still largely unresolved, which is why the starting points of the disruptive factors are still unknown. This dysfunction is a postmicrosomal regurgitation jaundice with increased levels of both unconjugated and conjugated bilirubin. 

Biochemically, a change in structure relating to the mucopolysaccharides (neuraminic add ) and monohydroxy bile acids probably accounts for the formation of biliary thrombi. Some of the under-hydroxylated bile salts appear in crystalline form the bile becomes increasingly viscous and its flow is impeded. This defect in the excretion of bile salts culminates in dysfunctions in the secretion of bilirubin, which is why bilirubin is regurgitated into the blood. The bile which accmnulates in the bile ducts ultimately becomes mucous and white because of the reabsorption of bile pigments by the epitheha of the small bile ducts. 

Prince MI, Burt AD, Jones DE. Hepatitis and liver dysfunction with rifampicin therapy for pruritus in primary biliary cirrhosis. Gut 2002 50(3) 436-9. 

Nafcillin is primarily cleared by biliary excretion while dicloxacillin is eliminated by both kidney and biliary excretion. No dose adjustments are needed in the setting of renal or hepatic dysfunction. 

In addition to nutritional inadequacy, vitamin deficiency may result from malabsorption, effects of pharmacological agents, and abnormalities of vitamin metabolism or utilization. Thus, in biliary obstruction or pancreatic disease, the fat-soluble vitamins are poorly absorbed despite adequate dietary intake because of steatorrhea. Absorption, transport, activation, and utilization of vitamins require the participation of enzymes or other proteins whose synthesis is under genetic control. Dysfunction or absence of one of these proteins can produce a disease that is clinically indistinguishable from one caused by dietary deficiency. In vitamin-dependent or vitamin-responsive... 

Answer B. Erythromycin is eliminated largely via biliary excretion, and decreases in renal function do not usually require a dosage reduction unless creatinine clearance <10 mL/min, All of the other antimicrobial drugs listed are eliminated by the kidney, at rates proportional to creatinine clearance, so major dose reductions would be needed in patients with renal dysfunction to avoid toxicity. 

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