Resin, bile

Combination drug therapy is an effective means to achieve greater reductions in LDL cholesterol (statin + ezetimibe or bile acid resin, bile acid resin + ezetimibe, or three-drug combinations) as well as raising HDL cholesterol and lowering serum triglycerides (statin + niacin or fibrate). 

Cholestyramine, colestipol, and colesevelam are the bile acidbinding resins or sequestrants (BAS) currently available in the United States. Resins are highly charged molecules that bind to bile adds (which are produced from cholesterol) in the gut. The resin-bile acid complex is then excreted in the feces. The loss of bile causes a compensatory conversion of hepatic cholesterol to bile, reducing hepatocellular stores of cholesterol resulting in an up-regulation of LDL receptors to replenish hepatocellular stores which then result in a decrease in serum cholesterol. Resins have been shown to reduce CHD events in patients without CHD.26... 

Anion-exchange resins (bile acid sequestrants)... 

In addition to the statin drugs which inhibit HMG-CoA reductase a number of other drugs are used to lower cholesterol levels. The first are resins which are also referred to as bile acid sequestrants such as cholestyramine. The resins work by binding to the bile acids followed by excretion of the resin-bile complex. To make up for the loss of the bile acids the body converts cholesterol into bile acids thus reducing the cholesterol levels. 

THERAP CAT Ion-exchange resin (bile salts) antihyper-... 

Hazardous Decomp. Prods. Toxic fumes of CO, CO2, NOx, hydrogen chloride gas Storage Hygroscopic store under ambient temps. protect from moisture Uses Ion-exchange resin (bile salts) antihyperlipoproteinemic antipruritic antidiarrheal reduces cholesterol will bind bile... 

The enterohepatic circulation can be interrupted by anticholesterol agents. These are positively charged resins that bind to the negatively charged bile salts. The resin/bile salt complex is egested in the faeces. 

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). 

Anion exchange resins are basic polymers with a high affinity for anions. Because different anions compete for binding to them, they can be used to sequester anions. Clinically used anion exchange resins such as cholestyramine are used to sequester bile acids in the intestine, thereby preventing their reabsorption. As a consequence, the absorption of exogenous cholesterol is decreased. The accompanying increase in low density lipoprotein (LDL)-receptors leads to the removal of LDL from the blood and, thereby, to a reduction of LDL cholesterol. This effect underlies the use of cholestyramine in the treatment of hyperlipidaemia. 

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

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. 

The answer is a. (Katzung, p 590.) Bile acids are absorbed primarily in the ileum of the small intestine. Cholestyramine binds bile acids, preventing their reabsorption in the jejunum and ileum. Up to 10-fold greater excretion of bile acids occurs with the use of resins. The increased clearance leads to increased cholesterol turnover of bile acids. Low-density lipoprotein receptor upregulation results in increased uptake of LDL. This does not occur in homozygous familial hypercholesterolemia because of lack of functioning receptors. 

Increased intake of soluble fiber in the form of oat bran, pectins, certain gums, and psyllium products can result in useful adjunctive reductions in total and LDL cholesterol (5% to 20%), but these dietary alterations or supplements should not be substituted for more active forms of treatment. They have little or no effect on HDL-C or triglyceride concentrations. These products may also be useful in managing constipation associated with the bile acid resins (BARs). 

Bile Acid Resins (Cholestyramine, Colestipol, Colesevelam)... 

BARs, bile acid resins fibrates include gemfibrozil or fenofibrate. 

In a small round-bottomed flask the ethereal mother liquor is concentrated to a volume of 10 c.c., 50 c.c. of low-boiling petrol ether are added, and the stoppered flask is shaken continuously until a clear solution is obtained. The petrol ether which is now poured out contains/uWy adds and cholesterol, whereas the bile acids formerly in solution in the ether have separated as a thick resinous mass. In order to separate the fatty acids and the cholesterol the petrol ether solution is carefully shaken with 50 to 60 c.c. of 2iV-potas-sium hydroxide solution. This solution is added in 10 c.c. portions, and each portion is at once removed so as to avoid emulsions. 

Adults in developed countries may consume about 40 g of such starch and between 10 and 20 g of fibre each day. Certain types of dietary fibre increase die faecal loss of bile salts. The loss can be increased artificially by the administration of ion exchange resins diat bind the bile salts. This is one means of lowering die liver and blood levels of cholesterol (Box 4.2). 

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. 

More recent approaches have used resin extractions, initially the nonionic resin XAD2 and XAD7. These resins are effective where the pH was kept at 10 while mixing the plasma and resin. The supernatant is discarded and the bile... 

Bile-acid sequestrants are indigestible, positively charged resins that bind negatively charged bile acids in the lumen of the intestine (reviewed in ref. 34). 

If the findings relating to obesity and improved glycaemic control can be confirmed in human studies such drugs would be highly attractive. As discussed above, bile-acid sequestrants have been used for many years to treat dyslipi-demia in relation to reducing cardiovascular disease risk and the safety profile of these compounds is well established. However, due to the large doses of compound that require to be consumed, compliance is an issue for BAS therapies. In the future, this may be resolved with the development of more specific and efficient resins that require lower doses. 

Cholestyramine (Cuemid, Dowex 1-X2-C1, Questran) is a quaternary ammonium cationic resin used primarily to bind, in the gut, bile salts which appear to be the main cause of pruritis in obstructive hepatic disease. Again, many unexpected facets of steroid and lipid metabolism are becoming clear following studies of the drug s effects [451.452]. 

Drugs (B). Colestyramine and colestipol are nonabsorbable anion-exchange resins. By virtue of binding bile acids, they promote consumption of cholesterol for the synthesis of bile acids the 2000 Thieme... 

Applications of cation and anion resins are varied and include purification of sugar, identification of drugs and biomacromolecules, concentration of uranium, calcium therapy to help increase the amount of calcium in our bones (i.e., increase the bone density), and use as therapeutic agents for the control of bile acid and gastric acidity. In the latter use, a solid polyamide (Colestid) is diluted and taken with orange juice, which facilitates removal of bile acids from the body. This removal helps the body to produce more bile acid from cholesterol, thus effectively reducing the cholesterol level. 

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