Cholestyramine diet

A patient in the medical clinic is taking cholestyramine (Questran) for hyperlipidemia. The primary health care provider has prescribed TLC for the patient. The patient is on a low-fat diet and walks daily for exercise. His major complaint at this visit is constipation, which is very bothersome to him. Discuss how you would approach this situation with the patient. What information would you give the patient concerning his constipation ... 

During the first day after each dose, 20% was excreted into urine, 0.5% into feces, and 20% into bile. The addition of 4% cholestyramine to diets for 6 days resulted in increased fecal excretion by a factor of 18 and increased total body burden excretion by 1.4 times (Rozman etal. 1982)... 

Trautwein, E. A., Siddiqui, A., and Hayes, K. C. (1993). Modeling plasma lipoprotein-bile lipid relationships Differential impact of psyllium and cholestyramine in hamsters fed a lithogenic diet. Metabolism 42,1531-1540. 

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). 

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. 

Rat colon Bile adds Cholestyramine High fat diets Wounding... 

Rozman KK, Rozman TA, Williams J, et al. 1982. Effect of mineral oil and/or cholestyramine in the diet on biliary and intestinal elimination of 2,4,5,2, 4, 5 -hexabromodiphenyl in the Rhesus monkey. J Toxicol Environ Health 9 611-618. 

A meta-analysis was performed on randomized trials assessing lipid-lowering therapy in 698 patients with PAD who were treated with a variety of therapies, including diet, cholestyramine, probucol, and nicotinic acid, for four months to three years (8). There was a significant difference in total mortality [0.7% in the treated patients, as compared with 2.9% in the patients given placebo (p = NS)], with an additional reduction in disease progression, as measured by angiography and the severity of claudication. 

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-... 

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)... 

The Lipid Research Clinics Coronary Primary Prevention Trial (L16, L17) is a landmark double-blind study in which cholestyramine, a bile acid se-questrant that is not absorbed from the gut, was used to lower plasma cholesterol. The investigators recruited 3806 men, with a Type II hyperlipoproteinemia phenotype and in good health, into the study. All were prescribed a cholesterol-lowering diet. Subjects were randomly assigned to a treatment group (who were prescribed 24 g cholestyramine daily) and a group with similar baseline characteristics who received an inactive placebo. A 19% lower incidence of coronary heart disease over a mean of 7.4 years in... 

It is clear from Equation (19.4) that saturated fat, not cholesterol, is the single most important factor that raises serum cholesterol. Some cases of hyperlipoproteinemia type IV (high VLDL) respond to low-carbohydrate diets, because the excess of VLDL comes from intestinal cells, where it is produced from dietary carbohydrate. Resins, such as cholestyramine and cholestipol, bind and cause the excretion of bile salts, forcing the organism to use more cholesterol. Lovastatin decreases endogenous cholesterol biosynthesis (see later), and niacin (nicotinic acid) apparently decreases the production of VLDL and, consequently, LDL. It also results in an HDL increase. Antioxidants that inhibit the conversion of LDL to oxidized LDL have also been used with some success. These are high doses of vitamin E and the drug probucol. 

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

Therapeutic uses The bile acid binding resins are the drugs of choice (often in combination with diet or niacin) in treating Type lla and lib hyperlipidemias. [Note In those rare individuals who are homozygous for Type lla, that is, for whom functional LDL receptors are totally lacking, these drugs have little effect on plasma LDL levels.] Cholestyramine can also relieve pruritus caused by accumulation of bile acids in patients with biliary obstruction. 

Cholestyramine may prove necessary for severe pruritus due to a cholestatic course of disease (4-8 g prior to breakfast) - if antihistamines were unsuccessful. With such a cholestatic course of disease, the application of ursodeoxycholic acid (2-3 x 250 mg) is most suitable. (166) In some cases with a fulminant course, interferon alpha has been successfully used. Special diets , glucocorticoids or other medication are not necessary. 

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-... 

Cholestyramine resin is the drug of choice for type lla hyperlipoproteinemia. When used in conjunction with a con-iFullcd diet, it reduces lipoproteins. The drug is an insoluble polymer and. thus, probably one of the safest because it is not absorbed from the gastrointestinal tract to cause systcmic losic effects. 

The mechanism of the inhibition of the HMG-CoA reductase by bile adds shown in Fig. 14 is a matter of controversy. Weis and Dietschy did not observe any influence of taurocholate on cholesterol synthesis in bile fistula rats fed a cholesterol-free diet, and concluded that the inhibitory effect of bile acids on cholesterol synthesis may be related to the increased absorption of cholesterol by the presence of bile acids in the intestine [247]. However, Hamprecht et al. were able to demonstrate a reduction of HMG-CoA reductase activity in lymph fistula rats infused with cholate [248]. Results by Shefer et al. also indicate that bile acids inhibit HMG-CoA reductase directly [212]. It seems likely that the inhibitory effect of the bile acids on HMG-CoA reductase may involve both direct and indirect effects. It was recently established that the stimulation of HMG-CoA reductase activity in response to treatment with cholestyramine is associated with an increase of the specific mRNA [258]. 

Schwardt et al (28) compared results after a self-selected diet alone, with cholestyramine added and with cholestyramine and 12 g apple pectin added for 12 weeks. Compared to the subjects self-selected diet alone, the addition of pectin plus cholestyramine decreased cholesterol 31% and LDL levels 35%, while the addition of only cholestyramine decreased cholesterol 19% and LDL levels 22%. Neither the HDL ratio nor triglycerides changed significantly from the prestudy levels. 

Cholestyramine is indicated as adjunctive therapy to diet for the reduction of elevated serum cholesterol in patients with primary hypercholesterolemia (elevated low-density lipoprotein [LDL] cholesterol) who do not respond adequately to diet. Similarly, it is indicated for the relief of pruritus associated with partial biliary obstruction. Cholestyramine is not absorbed but binds to bile acids in the intestine, whereupon it is eliminated. To replenish the lost bile acid, cholesterol is then converted to bile acid, and this lowers the level of cholesterol (see Figure 34). Cholestyramine has also been used in the treatment of cholestasis to control the intense pruritis. It reduces the LDL level in 4 to 7 days, and the maximum effect is seen in 14 days. 

Cholestyramine (Questran) Forms insoluble complex with bile salts, excreted in feces. Body compensates by increasing LDL receptors and oxidizing cholesterol to bile acids. LDL > 190 mg/dl (160 with 2 risk factors) provided that 6 month trial of low lipid diet has failed. i Cholesterol, LDL T Triglycerides, VLDL, HDL ... 

McAnena OJ, <%e JA, Daly JM Alteration of methotrexate metabolic in rats 1 administration of an elemental liquid diet. II. Reduced toxicity and improved survival using cholestyramine. Cancer 9Z7) 59,109I-7. 

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