Cholesterol cholestyramine effect

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. 

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). 

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 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. 

Compliance-related effects of cholestyramine on plasma cholesterol levels and risk of coronary events... 

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. 

Several other agents have beneficial effects on plasma lipid profiles occurring through various cellular mechanisms.89 Cholestyramine (Questran), for example, attaches to bile acids within the gastrointestinal lumen and increases the fecal excretion of these acids. This action leads to decreased plasma cholesterol concentrations because cholesterol breakdown is accelerated to replace the bile acids that are lost in the feces. 

Hypercholesterolemia is associated with abnormal vascular reactivity (Vita et al, 1990 Seiler et al., 1993), and there is some evidence that lipid lowering with HMG-CoA reductase inhibitors (Treasure et al., 1995 O Driscoll et al., 1997 Simons et al., 1998) and cholestyramine (Leung et al., 1993) can partially reverse this effect within a few months. Improvement in endothelial-dependent vasodilation has also been observed within 24 hours after LDL apheresis in patients with familial hypercholesterolemia this supports the view that high plasma concentrations of LDL adversely affect endothelial function and impair vasodilation (Tamai et al, 1997). However, the Coronary Artery Reactivity After Treatment with Simvastatin (CARATS) study, a large, well-controlled study, provided no evidence for an effect, despite a mean 40% reduction in LDL cholesterol with simvastatin 40 mg daily (Hodgson et al, 1996 Vita et al, 2000). Furthermore, a link between vascular reactivity and coronary events has yet to be established. 

Over the past few years noninvasive techniques for visualizing plaques in vivo have been refined, so that it has become possible to demonstrate a positive effect of cholesterol-lowering, in a secondary prevention trial with cholestyramine and a cholesterol-lowering diet, on coronary artery disease as assessed by angiography (L13)... 

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. 

The reabsorption of bile is impeded by oral administration of positively charged polymers, such as cholestyramine, that bind negatively charged bile salts and are not themselves absorbed. Cholesterol synthesis can be effectively blocked by a class of compounds called statins (e.g., lovastatin, which is also called mevacor Figure 26.22). These compounds are potent competitive inhibitors (AT j < 1 nM) of HMG-CoA reductase, the essential control point in the biosynthetic pathway. Plasma cholesterol levels decrease by 50% in many patients given both lovastatin and inhibitors of bile-salt reabsorption. Lovastatin and other inhibitors of HMG-CoA reductase are widely used to lower the plasma cholesterol level in people who have atherosclerosis, which is the leading cause of death in industrialized societies. 

Bile-acid-binding resin results in an interruption of the eiiterohepatic circulation of bile salts and in their iitcreased excretion in the feces. This drug therapy can pnsduce a 20-25" decrease in plasma LDL-cholesterol. A side effect of cholestyramine is constipation, but this problem can be relieved by a high fiber diet. 

One possible method to interrupt the feedback effect of bile acids in the liver is to administer, along with vitamin C, cholestyramine (Questran), a synthetic resin that binds bile acids in the gastrointestinal tract. If a moderate hypercholesterolemia is provoked in guinea pigs through a marginal vitamin C deficiency and then 1.5% of Questran (i.e., 0.66% of cholestyramine) is added to their diet, the level of cholesterol in blood serum remains unaffected. The simultaneous adminis-... 

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). 

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