Cholesterol cholestyramine

The human body tunts over about 800 mg of cholesterol per day. Most of this turnover (synthesis, degradation, or loss from the body) inv olves bile salts. More specifically, about 400 mg cholesterol is used to manufacture new bile salts to replace those that have been lost in the feces. About 80 mg cholesterol is lost through the skin about 50 mg is used for synthesis of steroid hormones. Cholestyramine can stimulate the loss of much more than the equivalent of 400 mg, and can produce clinically significant decreases in serum cholesterol Cholestyramine alone does not drastically lower serum cholesterol, because the liver senses any depletion and responds by increasing its rate of cholesterol biosynthesis. However, use of the drug in combination with other drugs that Inhibit... 

In contrast to the extensive literature on the regulation of intestinal cholesterol synthesis, only a few studies are available on regulation of lipoprotein uptake in this organ. Notably, recent studies have compared the effect of various interventions such as the feeding of cholesterol, cholestyramine, surfomer, and com oil on both rates of cholesterol synthesis and LDL transport in the rat intestine in vivo, as shown in Fig. 9. While these various manipulations all alter rates of cholesterol synthesis, there is no consistent effect upon LDL uptake at any location in the mucosa, with the possible exception of a slight increase in the jejunum after feeding... 

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. 

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... 

A 45-year-old male takes simvastatin for hypercholesterolemia however, his cholesterol level remains above target at maximal doses. Cholestyramine is added to the therapeutic regimen. What drug-drug interaction can occur ... 

A 40-year-old male with markedly elevated cholesterol, diagnosed as having heterozygous familial hypercholesterolemia, is treated with cholestyramine. What is the mechanism of action of 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. 

Cholesterol-phospholipid-lipoprotein liquid crystal phase, 15 112 Cholestyramine, 14 420... 

Cholestyramine, a chelating agent, binds chlordecone present in the gastrointestinal tract and limits its enterohepatic recirculation (Boylan et al. 1978 Cohn et al. 1978). This interaction leads to increased excretion of the chlordecone and decreased toxicity. Thus, persons being treated with cholestyramine to lower plasma cholesterol may experience increased excretion of chlordecone and decreased toxicity. The use of cholestyramine as a therapeutic agent in cases of chlordecone poisoning is discussed more fully in Section 2.8.2, Reducing Body Burden. 

Matheson, H. B., Colon, I. S., and Story, J. A. (1995). Cholesterol 7a-hydroxylase activity is increased by dietary modification with psyllium hydrocolloid, pectin, cholesterol and cholestyramine in rats. /. Nutr. 125,454-M58. 

Treatment of Hypercholesterolemia Cholestyramine and other drugs that increase elimination of bile salts force the liver to increase their synthesis from cholesterol, thus lowering the internal level of cholesterol in the hepatocytes. Decreased cholesterol within the cell increases LDL receptor expression, allowing the hepatocyte to remove more LDL cholesterol from the blood. HMG-CoA reductase inhibitors such as lovastatin and simvastatin inhibit de novo cholesterol synthesis in the hepatocyte, which subsequently increases LDL receptor expression. 

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. 

The laboratory must be informed when the therapeutic regimens include drugs specifically administered to change the blood level of a biochemical constituent. Cholestyramine resin, a nonabsorbable anion exchange resin administered orally to patients with hyperlipoproteinemia produced a 24% decline in serum cholesterol levels in 14 patients with essential hypercholesterolemia. In these patients the mean cholesterol fell from 414 98 mg/100 ml to 176 21 mg/100 ml (FI). Pectin added to the diet caused a 5% decrease in serum cholesterol values (K4), as did an oral hydrophobic colloid (G4). Levels fell in one case from 220 mg/ 100 ml to 160 mg/100 ml (G4). Nicotinic acid, neomycin, and p-chloro-phenoxyisobutyrate have all been used to reduce serum cholesterol (G7). 

Superior to fibrates, cholestyramine, and probucol in lowering total and LDL cholesterol levels... 

The answer is a. (Hardman, pp 875-898.) In type I hyperlipoproteinemia, drugs that reduce levels of lipoproteins are not useful, but reduction of dietary sources of fat may help. Cholesterol levels are usually normal, but triglycerides are elevated. Maintenance of ideal body weight is recommended in all types of hyperlipidemia. Clofibrate effectively reduces the levels of VLDLs that are characteristic of types 111, IV, and V hyperlipoproteinemia administration of cholestyramine resin and lovastatin in conjunction with a low-cholesterol diet is regarded as effective therapy for type 11a, or primary, hyperbetalipoproteinemia, except in the homozygous familial form. 

In addition to treatment with the statins, hypercholesterolemia is sometimes treated with the use of nonabsorbable anion-exchange resins like cholestyramine (5.13) and colestipol, which sequester bile acid in the intestine, excrete them, and thus increase their synthesis in the liver by a feedback mechanism. Increased bile acid synthesis increases cholesterol metabolism and also decreases LDL concentrations. Unfortunately, these resins interfere with the absorption of other fats and fat-soluble vitamins (A, D, E, and K). They... 

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