Cholestyramine cirrhosis

Uses Edema, HTN, CHF, h atic cirrhosis Action Loop diuretic -1- reabsorption of Na Cr in ascending loop of Henle distal tubule Dose 5-20 mg/d PO or IV 200 mg/d max Caution [B, ] Contra Sulfonylurea sensitivity Disp Tabs, inj SE Orthostatic -1- BP, HA, dizziness, photosens, electrolyte imbalance, blurred vision, renal impair Notes 20 mg torsemide = 40 mg furosemide Interactions t Risk of ototox W/ aminoglycosides, cisplatin t effects W/ thiazides t effects OF anticoagulants, antih5rpCTtensives, Li, salicylates X effects IT/barbiturates, carbamaz ine, cholestyramine, NSAIDs, phenytoin, phenobarbital, probenecid, dandehon EMS t Effects of anticoagulants monitor for S/Sxs tinnitus, monitor ECG for hypokalemia (flattened T waves) OD May cause HA, hypotension, hypovolemia, and hypokalemia give IV fluids symptomatic and supportive... 

Biliary cirrhosis, secondary disease this requires elimination of the obstructive cause. Itching associated with bile acid retention can respond to cholestyramine, a bile acid binding resin. 

Biliary obstruction due to stone, tumor, or primary biliary cirrhosis Zollinger-Ellison syndrome (causes hyperacidity) bacterial overgrowth and stasis administration of drugs, neomycin, and cholestyramine Ileal disease or resection... 

Cholestyramine resin also is helpful for the relief of pruritus associated with partial biliary obstruction and in conditions such as primary biliary cirrhosis. Cholestyramine increases fecal excretion of bile acids and reduces circulating and eventually systemic levels with relief of pruritus in -1-3 weeks. 

Bile acid sequestrants are indicated for the treatment of hypercholesterolemia in patients who do not adequately respond to dietary modifications. They may be used either alone or in combination with HMGRIs or niacin. These combinations often can achieve a 50% reduction in plasma LDL levels. Cholestyramine, but neither colestipol nor colesevelam, also is approved for the relief of pruritus associated with partial biliary obstruction. Bile acid sequestrants should not be used to treat hypertriglyceridemias or mixed hyperlipoproteinemias in which hypertriglyceridemia is the primary concern. These compounds also are contraindicated in patients with cholelithiasis or complete biliary obstruction because of the impaired secretion of bile acids caused by these conditions. Finally, cholestyramine and colestipol are contraindicated in patients with primary biliary cirrhosis, because this can further raise serum cholesterol (7,15,21). 

Bile acids have two major functions in man (a) they form a catabolic pathway of cholesterol metabolism, and (b) they play an essential role in intestinal absorption of fat, cholesterol, and fat-soluble vitamins. These functions may be so vital that a genetic mutant with absence of bile acids, if at all developed, is obviously incapable of life, and therefore this type of inborn error of metabolism is not yet known clinically. A slightly decreased bile acid production, i.e., reduced cholesterol catabolism, as a primary phenomenon can lead to hypercholesterolemia without fat malabsorption, as has been suggested to be the case in familial hypercholesterolemia. A relative defect in bile salt production may lead to gallstone formation. A more severe defect in bile acid synthesis and biliary excretion found secondarily in liver disease causes fat malabsorption. This may be associated with hypercholesterolemia according to whether the bile salt deficiency is due to decreased function of parenchymal cells, as in liver cirrhosis, or whether the biliary excretory function is predominantly disturbed, as in biliary cirrhosis or extrahepatic biliary occlusion. Finally, an augmented cholesterol production in obesity is partially balanced by increased cholesterol catabolism via bile acids, while interruption of the enterohepatic circulation by ileal dysfunction or cholestyramine leads to intestinal bile salt deficiency despite an up to twentyfold increase in bile salt synthesis, to fat malabsorption, and to a fall in serum cholesterol. 

Cholesterol and fat-soluble vitamins require bile acid induced micellar solubilization for absorption, which takes place in the upper small intestine (c/. 32,116-118). Accordingly, in bile salt deficiency states, cholesterol absorption should be markedly impaired and fecal neutral sterol excretion increased. The fact that fecal neutral steroid excretion on a low-cholesterol diet is actually normal, as after ileal resection, ileal bypass, and cholestyramine treatment, or even decreased, as in cirrhosis of the liver or biliary occlusion (11), is due to a markedly reduced biliary secretion of cholesterol. In gluten enteropathy, in which no excessive bile salt loss usually exists, fecal neutral sterol excretion is markedly augmented (119). However, in occasional cases in which fecal bile salt elimination is markedly enhanced, the fecal neutral steroid excretion is quite normal, probably owing to decreased biliary cholesterol secretion as a consequence of low biliary bile salt secretion. Detailed information on the role of bile salts in both intraluminal and mucosal phases of fat and sterol absorption is presented in many recent reviews (6,10,113,114,117). 

Fecal bile acid elimination is markedly reduced in patients with liver cirrhosis (11,182,191), even if icterus and signs of biliary obstruction are absent (11,182). Since, in addition, the urinary excretion of bile acids is quantitatively, if not proportionally (81), negligible, it can be concluded that the overall bile acid synthesis is markedly depressed in liver cirrhosis (182). The administration of cholestyramine, which is associated with reduction of both serum bile acids (188,192,193) and urinary bile acids (88,182), augmented the fecal bile acid excretion to a very small extent only (182). This indicates that the ability of the parenchymal cells to increase their bile acid production is clearly decreased compared to that of normal subjects. Though the fecal neutral sterol excretion was also increased by cholestyramine, only a relatively small decrease in serum cholesterol was found, suggesting that the patients still were able to increase their cholesterol production (182). 

Lithocholic acid has been associated with the development and progression of human liver cirrhosis (188,202). This acid is found in human serum, particularly in cirrhotic patients (202,210), in whom chenodeoxycholic acid is the predominant bile acid. Serum lithocholic acid is decreased by cholestyramine and neomycin in cirrhosis, and it has been suggested that the treatment of cirrhotic patients with these drugs warrants consideration (202). Usually, however, the correlation between the levels of lithocholic acid and its precursor chenodeoxycholic acid is poor (188,193). Long-term treatment of patients with lithogenic bile with chenodeoxycholic acid led to an almost complete predominance of this bile acid in bile, yet the amount of lithocholic acid was not increased significantly (96). Predominance of chenodeoxycholic acid appears to be related to the parenchymal cell function (195) the poorer it is the more predominant is chenodeoxycholic acid among the bile acids. However, a simultaneous decrease of hepatic secretory function possibly associated with intrahepatic biliary obstruction reduces the quantitative flow of chenodeoxycholate to the colon, so that bacterial formation and... 

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