Bile acid binding

Bile Acid Sequestrants. The bile acid binding resins, colestipol [26658424] and cholestyramine, ate also effective in controlling semm cholesterol levels (150). Cholestyramine, a polymer having mol wt > ICf, is an anion-exchange resin. It is not absorbed in the gastrointestinal tract, is not affected by digestive enzymes, and is taken orally after being suspended in water (151). 

Hyperlipidemia. Bile acid binding resins such as cholestyramine sequester bile acids in the intestine,... 

Within the small intestine, bile-acid binding interferes with micelle formation. Nauss et al. [268] reported that, in vitro, chitosan binds bile acid micelles in toto, with consequent reduced assimilation of all micelle components, i.e., bile acids, cholesterol, monoglycerides and fatty acids. Moreover, in vitro, chitosan inhibits pancreatic lipase activity [269]. Dissolved chitosan may further depress the activity of lipases by acting as an alternative substrate [270]. 

The answer is c. (Hardman, pp 887, 889.) Bile acid-binding resins bind more than just bile acids, and binding of simvastatin to cholestyramine is the most likely mechanism for decreased Gl absorption. Cholestyramine may also bind to several other drugs, including digoxin, benzothiadiazides (thiazides), warfarin, vancomycin, thyroxine (T4), and aspirin. Medications should be given one hour before or four hours after cholestyramine. 

Drugs Drugs that lower the blood levels of cholesterol are frequently used as part of the treatment these include (i) Oral bile acid binding exchange resins. Resins such as cholestyramine are effective because, when taken by mouth, they prevent the reabsorption of bile acids in the lower small intestine, so that they are excreted in the faeces. Since bile acids are formed in the liver from cholesterol, synthesis of more acids requires more cholesterol uptake by the liver from the blood, which occurs via LDL-cholesterol, so that the concentration of the latter is decreased. 

Intestinal bile-acid-binding protein (IBABP) is a small 14-15-kDa protein found in the cytoplasm of cells in the ileum that binds bile acids as they enter the cell. By using photolabile bile-acid derivative and immunoprecipitation, expression was primarily found in the soluble protein fraction of ileal enter-ocytes, although cholangiocytes do show a low level of expression. One molecule of IBABP binds two bile-acid molecules as shown in Figure 2.4. 

IBABP intestinal bile-acid-binding protein... 

Figure 7.4 The effect of bile acids on energy expenditure. Circulating bile acids bind to the G-protein-coupled receptor, TGR5 that stimulates increased cAMP-PKA activation and increased expression of type-2 iodothyronine deiodinase (D2). This response is sensitised by a high-fat diet. D2 converts thyroxine (T4) to active 3,5,3 -tri-iodothyronine (T3). T3 stimulates thyroid hormone receptor binding to target genes. This leads to altered expression of genes associated with energy balance, and increased energy expenditure.

Currently available BAS include cholestyramine, colestipol and colesevelam hydrochloride (colestimide). Cholestyramine comprises a long-chain polymer of styrene with divinylbenzene trimethylbenzylammonium groups, whereas colestipol is a long-chain polymer of l-chloro-2,3-epoxypropane with diethylenetriamine. Colesevelam HCl is poly(allylamine hydrochloride) cross-linked with epichlorohydrin and alkylated with 1-bromodecane and 6-bromo-hexyl-trimethylammonium bromide. Bile-acid binding is enhanced and stabilised in the latter compound by long hydrophobic sidechains, increased density of primary amines, and quaternary amine sidechains. For this reason, colesevelam HCl exhibits increased affinity, specificity and capacity to bind bile acids compared with the other BAS. Colesevelam HCl also binds dihydroxy and trihydroxy bile acids with equal affinity, contrasting with cholestyramine and colestipol that preferentially bind dihydroxy bile acids (CDCA and deoxycholic acid). The latter BAS can lead to an imbalance towards trihydroxy bile acids and a more hydrophilic bile-acid pool. 

Concomitant lipid-lowering f/ erapy-Atorvastatin may be used in combination with a bile-acid-binding resin for additive effect. Generally, avoid the combination of HMG-CoA reductase inhibitors and fibrates. 

Concomitant lipid-lowering therapy-The effect of rosuvastatin on LDL-C and total-C may be enhanced when used in combination with a bile acid-binding resin. If rosuvastatin is used in combination with gemfibrozil, limit the dose of rosuvastatin to 10 mg once daily. 

In addition symptomatic treatment with opiates, with bile acid binding resins in those with bile acid malabsorption, with milk free diets in those who are lactose intolerant, and with low fat diets may materially help relevant symptoms. 

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. 

Itching associated with retention of bile acids is ameliorated by treatment with the bile acid binding resin cholestyramine. Fat soluble vitamin (A, D and K) deficiency may require administration of supplements. Direct toxic effects of alcohol associated with dietary deficiency may require soluble B vitamin administration. 

The bile acid-binding agents are large polymeric cationic exchange resins that are insoluble in water. They bind bile acids in the intestinal lumen and prevent their reabsorption. The resin itself is not absorbed. 

FIBRIC ACID DERIVATIVES BILE ACID-BINDING RESINS... 

Colestimide (colestilan)2 Bile acid binding resin improves glycemic control and reduces weight in an obese DM-2 model... 

See also Antacids Bile acid-binding resins. 

Review of the use of HMG-CoA inhibitors and bile acid-binding resins to reduce serum cholesterol. 

Fibric Acid Derivatives Bile Acid-Binding Resins... 

Bile acid-binding Resins may bind with orally... 

Bile acid binding resins have been the mainstay of treatment for heterozygous FH for many years. Unfortunately they are not as effective as one might hope, because the liver partially compensates for the drain on cholesterol by increasing its own production of cholesterol from acetyl-CoA (B51, Dll). Two recently developed drugs, compactin (B50, E7) and mevinolin... 

There are four principal classes of lipid-lowering drugs used in the treatment of CAD (1) 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, (2) bile acid-binding resins, (3) nicotinic acid, and (4) fibric acid derivatives. 

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