Cholesterol colestipol

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). 

Cliolestyramine (Questran) and colestipol (Colestid) are examples of bile acid sequestrants. Bile, which is manufactured and secreted by the liver and stored in the gallbladder, emulsifies fat and lipids as these products pass through the intestine Once emulsified, fats and lipids are readily absorbed in the intestine These drug bind to bile acids to form an insoluble substance that cannot be absorbed by the intestine, so it is secreted in the feces. With increased loss of bile acids, the liver uses cholesterol to manufacture more bile This is followed by a decrease in cholesterol levels. 

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... 

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... 

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... 

Colestipol Binds bile acids in gut prevents reabsorption increases cholesterol catabolism up-regulates LDL receptors Decreases LDL Elevated LDL, digitalis toxicity, pruritus Oral taken with meals not absorbed Toxicity Constipation, bloating interferes with absorption of some drugs and vitamins... 

Simvastatin (Zocor) [Anrilipemic/HMG-CoA Reductase Inhibitor] Uses X Cholesterol Action HMG-CoA reductase inhibitor Dose Adults. 5-80 mg PO w/ meals X in renal insuff Peds. 10-17 y 10 mg, 40 mg/daily max Caution [X, —] Avoid concurrent use of gemfibrozil Contra PRG, liver Dz Disp Tabs 5,10, 20, 40, 80 mg SE HA, GI upset, myalgia, myopathy (muscle pain, tenderness or weakness w/ creatine kinase 10 x ULN), Hep Interactions T Effects OF digoxin, warfarin T risk of myopathy/iiiabdomyolysis W/ amiodarone, cyclosporine, CYP3A4 inhibitors, fibrates, HIV protease inhibitors, macrolides, niacin, verapamil, grapefruit juice X effects W/ cholestyramine, colestipol, fluvas-tatin, isradipine, propranolol EMS T Effects of warfarin use amiodarone and... 

Ryan JR, Jain A. The effect of colestipol or cholestyramine on serum cholesterol and triglycerides in a long-term controlled study. J Clin Pharmacol New Drugs 1972 12(7) 268-73. 

Prior to 1987, the lipid-lowering armamentarium was limited essentially to dietary changes (reductions in saturated fats and cholesterol), the bile acid sequestrants (cholestyramine and colestipol), nicotinic acid (niacin), the fibrates, and probucol. Unfortunately, all of these treatments have limited efficacy or tolerability or both. Substantial reductions in LDL cholesterol (up to 47%) accompanied by increases in HDL cholesterol of up to 32% could be achieved by the combination of a lipid-lowering diet, a bile acid sequestrant, and the subsequent addition of nicotinic acid (Illingworth et al., 1981). However, this therapy is not easy to administer or tolerate and was therefore often unsuc-... 

Receptor numbers have been increased by the administration of cholestyramine or colestipol, bile acid sequestrants that diminish the bile acid pool, force the liver to convert more cholesterol into bile acids (Dll), lower the intracellular cholesterol in hepatic cells, and thus increase the number of hepatic B-100,E receptors (K25, S27). 

Bile acid sequestrates are anion-exchange resins, which sequester bile acid in the intestine. Cholestyramine and colestipol are the most commonly used in this category, which by this mechanism prevents bile acid re-absorption and causes decreased absorption of exogenous cholesterol and increased metabolism of endogenous cholesterol into bile acid in the liver by preventing enterohepatic recirculation. This leads to an increased expression of LDL receptors in liver and causes increased removal of LDL from blood and reduces the LDL cholesterol in the plasma. 

Treatment Low cholesterol and low saturated fat in the diet. Heterozygotes Cholestyramine or colestipol, and/or lovastatin or mevastatin. Homozygotes As above, plus niacin. 

Cholestyramine or colestipol (resins). These are compounds that bind bile acids the drop in hepatic reabsorption of bile acids releases a feedback inhibition, resulting in a greater amount of cholesterol being converted to bile acids to maintain a steady level in the circulation. Additionally, synthesis of LDL receptors increases to allow for the increased cholesterol uptake for bile acid synthesis the overall effect is a reduction in plasma cholesterol. 

Ion-exchange resins are now being used medicinally and as systems for modified release of dmgs (see Fig. 10.13). Colestyramine and colestipol are insoluble quaternary ammonium anion-exchange resins which, when administered orally, bind bile acids and increase their elimination because the high molecular weight complex is not absorbed. As bile acids are converted in vivo into cholesterol, colestyramine is used as a hypocholesteraemic... 

The polymeric ion-exchange resins cholestyramine and colestipol act by binding bile acids, preventing their reabsorption so promoting hepatic conversion of cholesterol into bile acids. This results in increased LDL-receptor activity of liver cells, which increases the break down of LDL-cholesterol. In this way the compounds effectively reduce LDL-cholesterol (but can aggravate hypertriglyceridaemia). 

A wide variety of pharmacological agents for cholesterol lowering in adults are available, including (1) bile acid-binding resins (cholestyramine and colestipol), (2) niacin. 

Ion exchange resins - The bile acid sequestering anion exchange resins (cholestyramine, colestipol and polidexide) continue to show utility in lowering serum cholesterol levels in Type II hyperlipoproteinemia." " "... 

Procetofene - In a 3-year trial in 340 patients with Types Ila, Ilb and IV hyperlipoproteinemia, procetofene ( 7) produced dose-dependent (200-400 mg/ day) decreases in serum cholesterol (20-36% reduction) in Type II patients and 20-50% decreases in serum triglycerides in Types lib and IV subjects. Colestipol plus procetofene produced greater reductions in... 

Structures of bile acid sequestrants. Cholestyramine and colestipol are hydrophilic yet water-insoluble, nondigestible, and nonabsorbable synthetic resins. They bind bile acids in the intestine to increase their loss in feces and thereby decrease plasma cholesterol levels. 

A combination of bile acid sequestrants with nicotinic acid or probucol or an HMG-CoA reductase inhibitor can be used to produce synergistic effects in lowering plasma lipoprotein levels, particularly LDL. The efficacy of drug treatment was shown in a recent study in which lovas-tatin and colestipol were used to reduce cholesterol levels in men with CHD. The rate of progression of coronary lesions was decreased and that of regression increased. These changes also were associated with reduced cardiovascular abnormalities. 

Cholestyramine, colestipol, and colesevelam fLDL catabolism 4-Cholesterol absorption 4-Cholesterol 4LDL fVLDL Problem with compliance binds many coadministered acidic drugs... 

Cholestyramine and colestipol are resins that complex bile salts, preventing their reabsorption from the GI tract —>4 feedback inhibition of 7 alpha hydroxylase —>T synthesis of new bile salts —liver cholesterol — T LDL receptors —plasma LDL. 

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