Cholestyramine administration

Cholestyramine is an ion-exchange resin that traps the bile salts and thereby secures their elimination in the intestine. The bile salts are continuously excreted in the intestine bile acid formation from cholesterol increases, and serum cholesterol levels drop. Existing evidence indicates that cholestyramine administration and ileal bypass are the most effective measures available to reduce serum cholesterol in hypercholesterolemic patients. 

The only relevant information located was that administration of cholestyramine resin may increase fecal excretion of endosulfan trapped in the enterohepatic circulation (Dreisbach and Robertson 1987 Howland 1990 HSDB 1999). 

Reduced folate Reduction of serum or red cell folate has been reported over long-term administration of cholestyramine. Consider supplementation with folic acid. 

Itching associated with retention of bile acids is ameliorated by treatment with the bile acid binding resin cholestyramine. Fat soluble vitamin (A, D and K) deficiency may require administration of supplements. Direct toxic effects of alcohol associated with dietary deficiency may require soluble B vitamin administration. 

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. 

PBBs and PBDEs tend to accumulate in lipid-rich tissues and are slowly metabolized and eliminated from the body (see Section 3.4). Several methods to enhance the elimination of PBBs from the body have been examined in animals and are also relevant to PBDEs, including the restriction of caloric intake (to reduce total body fat), and the administration of various agents that interact with bile acids including activated charcoal, mineral oil and bile-binding resins such as cholestyramine (Kimbrough et al. 1980 McConnell et al. 1980 Polin and Leavitt 1984 Polin et al. 1985, 1991 Rozman et al. 1982). It should be mentioned, however, that based on the pharmacokinetic considerations discussed in Section 3.8.1, a rapid breakdown... 

Concomitant administration of paracetamol with other hepatotoxic drugs or drugs acting on liver microsomal enzymes enhances paracetamol toxicity. Other drugs that interact with paracetamol are metoclopramide, probenecid, and cholestyramine.81... 

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). 

ANION EXCHANGE RESINS MYCOPHENOLATE 4- plasma concentrations of mycophenolate by approximately 40%. Risk of therapeutic failure Due to interruption of enterohepatic circulation because of binding of recirculating mycophenolate with cholestyramine in the intestine Avoid co-administration... 

LEFLUNOMIDE LIPID-LOWERING DRUGS-CHOLESTYRAMINE i levels of leflunomide 1 absorption Avoid co-administration... 

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. 

Treatment of icteric episodes with phenobarbital (3 x 20-60 mg/day) together with phototherapy (430-470 nm, 8-12 hr/day) and/or plasmapheresis is indicated. Cholestyramine (3x4 g/day) or cholestipol (3x5 g/day) may be used to treat pruritus. Qther recommended effective antipruritics are naloxone (2-3 x 0.4 mg/day, i.v.) or naltrexone (2-4 x 25-50 mg/day), which act as opi-oidergic neurotransmitters. (69) It is also possible to use the 5-HT3 antagonist ondansetron (3 x 4.8 mg/day, i.v. or orally). (64) Refractory cholestasis pruritus has recently been treated successfully with dronabinol (50) and also with sertraline. Administration of ursodeoxycholic acid (22, 53), medium-chain fatty acids, PUFA (65) and fat-soluble vitamins (especially vitamin K) is recommended. (s. pp 6, 47) (s. tab. 13.11)... 

The most important prophylactic measures for preventing the development of hepatic osteopathy are (i.) avoidance of harmful noxae (alcohol, nicotine), (2.) avoidance of risk factors (e. g. overweight calcium, phosphate or vitamin D deficiency use of glucocorticoids, cholestyramine and antacids containing aluminium), (2.) administration of vitamin K2 (menatetrenone) in women with risk factors, and (4.) routine physical exercise. (s. p. 650) We have instructed our chronic liver patients to carry out the following exercises on a regular basis ... 

Cholestyramine and Colestipol. Other interactions involving complexation might be anticipated when cholestyramine (e.g., Questran) and colestipol (Coles-tid) are used. These resinous materials, which are not absorbed from the GI tract, bind with bile acids and prevent their reabsorption. In addition, cholestyramine and colestipol can bind with drugs (e.g., digoxin and warfarin) that are present in the GI tract. To minimize the possibility of an interaction, the interval between the administration of cholestyramine or colestipol and another drug should be as long as possible. 

Consider vitamin supplementation and monitor iron status for long-term use of cholestyramine Ensure adequate calcium, vitamin D intake by spacing supplements at least 2 h from administration of cholestyramine... 

Thomas FB, Salsburey D, Greenberger NJ. Inhibition of iron absorption by cholestyramine. Demonstration of diminished iron stores following prolonged administration. Am J Dig Dis 1972 17(3) 263-9. 

Drug Interactions Various drugs can decrease T absorption. Drugs such as aluminum hydroxide, ferrous sulfate, sucralfate, and calcium carbonate should be separated from T administration by 1 to 2 hours. Bile acid sequestrants (cholestyramine and colestipol) must be separated from T by at least 4 hours and preferably 6 hours. CYP450 enzyme inducing drugs such as phenytoin, carba-mazepine, rifampin, and phenobarbital can increase T requirements. 

It has been suggested that the enterhepatobiliary cycle plays a role in the hepatic necrosis observed in bromobenzene toxicity. This is supported by the experimental findings that bromobenzene-induced hepatic necrosis can be prevented by the administration of cholestyramine. 

MPA usually reaches maximal concentrations within an hour of the time of oral administration of MME Distribution of the drug is rapid and essentially complete in most patients within 2 to 3 hours of administration. In whole blood, >99.9% of the drug is in the plasma compartment. MPAs clearance is affected by (1) glucuronidation, (2) enterohepatic circulation (EHC), and (3) the quantity of its free fraction. EHC is considered to be a significant contributor to the dose interval kinetics of MPA, especially the post-distribution phase of the concentration-time curve. The contribution of EHC to the MPA AUC is about 37%, ranging from 10% to 61%, based on the effect of concomitant administration of cholestyramine. The appearance of a secondary MPA concentration peak anywhere from 4 to 12 hours following the morning dose of MMF is believed to result from EHC. 

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