Bile acid sequestrants absorption

The bile acid sequestrants are contraindicated in patients with known hypersensitivity to the drugs. Bile acid sequestrants are also contraindicated in those with complete biliary obstruction. These drags are used cautiously in patients with a history of liver or kidney disease Bile acid sequestrants are used cautiously during pregnancy (Pregnancy Category C) and lactation (decreased absorption of vitamins may affect the infant). 

Bile acid sequestrants may interfere with die digestion of fats and prevent die absorption of die fat-soluble vitamins (vitamins A, D, E, and K) and folic acid. When die bile acid sequestrants are used for long-term therapy, vitamins A and D may be given in a water-soluble form or administered parenterally. If bleedingtendencies occur as die result of vitamin K deficiency, parenteral vitamin K is administered for immediate treatment, and oral vitamin K is given for prevention of a deficiency in the futum... 

As discussed above, obesity is associated with dyslipidemia, a condition where high levels of low-density lipoprotein cholesterol (LDL-C) is common. Elevated LDL-C is strongly associated with an elevated risk of coronary artery disease and for this reason a number of lipid-lowering therapies that target LDL-C have been developed. These include bile-acid sequestrants (BAS), statins (HMG-CoA reductase inhibitors), cholesterol absorption inhibitors, and fibrates. ... 

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. 

An opposite effect is at the basis of the up-regulation of LDL receptors in response to treatments with bile acid sequestrants, intestinal cholesterol absorption inhibitors, and HMG-CoA reductase inhibitors. The first class of drugs inhibits the intestinal reabsorption of bile acids, thus promoting increased conversion of cholesterol to bile acids in the liver. The increased demand for cholesterol results in activation of the SREBP system and upregulation of LDL receptor synthesis (as well as cholesterol synthesis via upregulation of HMG-CoA reductase). Similarly, inhibition of intestinal cholesterol absorption with ezetimibe results in a reduction in the hepatic cholesterol pool... 

The primary goal of therapy is the control of the hypercholesterolemia and prevention of atherosclerotic cardiovascular disease. Patients with heterozygous FH can usually be successfully treated with medications to lower the LDL cholesterol to acceptable levels (Table 14-2). They are generally responsive to treatment with statins, alone or in combination with other drugs, such as bile acid sequestrants (such as cholestyramine) or cholesterol absorption inhibitors (such as ezetimibe) that act additively to upregulate the expression of the functioning LDL receptor as described in the Biochemical Perspectives section. In a few cases, a more aggressive treatment with LDL apheresis (discussed in this section) may have to be considered in order to reach acceptable LDL cholesterol levels. 

Since bile acids are made from endogenous cholesterol, the enterohepatic circulation of bile acids may be disrupted as a way to lower cholesterol. Bile acid sequestrants bind bile acids in the gut, preventing their re-absorption. In so doing, more endogenous cholesterol is directed to the production of bile acids, thereby lowering cholesterol levels. The sequestered bile acids are excreted in the faeces. 

Bile acid sequestrants should be used with caution in constipation and avoided in complete biliary obstruction or in patients at risk of decompensation. Vitamin K absorption may be reduced and the INR/PT should be monitored. Oral vitamin K supplementation should not be administered at the same time of day. There should be an adequate interval between the administration of bile acid sequestrants and other drugs. 

Absorption usually inhibition of absorption (e.g. bile acid sequestrants)... 

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. 

The most common drugs used to lower hepatic cholesterol by increasing the formation of bile acids do so by interrupting the enterohepatic circulation. These bile acid sequestrants (e.g., cholestyramine) are Insoluble resins that bind tightly to bile acids in the lumen of the intestines, forming complexes that prevent IBAT-medlated absorption by intestinal epithelial cells. The complexes are excreted in the feces. The resulting decrease in the return of bile acids to the liver causes a drop in the hepatic bile acid pool. As... 

These bind bile acids in the intestine, increasing their excretion by preventing entero-hepatic recycling. This in turn causes the liver to use endogenous cholesterol for bile acid synthesis and circulating LDL levels fall. In addition, since bile acids are needed for cholesterol absorption this is reduced as well. Examples of bile acid sequestrants are colestipol and cholestyramine. 

Statins Ezitimibe Omega-3 triglycerides Bile acid sequestrants Fibrates Nicotinic acid derivatives Inhibit HMG-CoA reductase Inhibits absorption of cholesterol from the intestine Inhibit VLDL synthesis in the liver Bind bile acids in the intestine Lower levels of circulating VLDLs and LDLs by unknown mechanism Reduce the release of VLDLs from the liver... 

Thiazide diuretics may diminish the effects of anticoagulants, uricosuric agents used to treat gout, sulfonylureas, and insulin and increase the effects of anesthetics, diazoxide, cardiac glycosides, hthium, loop diuretics, and vitamin D. The effectiveness of thiazide diuretics may be reduced by NSAlDs and bile acid sequestrants (reduced absorption of thiazides). Amphotericin B and corticosteroids increase the risk of hypokalemia induced by thiazide diuretics. 

Pravastatin (pravachol) therapy is started with a 20- or 40-mg dose that may be increased to 80 mg it should be taken at bedtime. Since pravastatin is a hydroxy acid, it is bound by bile-acid sequestrants, which reduce its absorption. This is rarely a problem since the resins should be taken before meals and pravastatin should be taken at bedtime. Pravastatin is also marketed in combination with buffered aspirin (PRAVIGARD). The small advantage of combining these two drugs should be weighed against disadvantages inherent in fixed-dose combinations. 

BILE ACID SEQUESTRANTS Cholestyramine, colestipol, and colesevalam effectively bind bile acids and some bacterial toxins. Cholestyramine is useful in the treatment of bile salt-induced diarrhea, as in patients with resection of the distal Ueum. In these patients, there is partial interruption of the normal enterohepatic circulation of bile salts, resulting in excessive concentrations reaching the colon and stimulating water and electrolyte secretion (see below). Patients with extensive ileal resection (usually >100 cm) eventually develop net bile salt depletion, which can produce steatorrhea because of inadequate micellar formation required for fat absorption. In such patients, the use of cholestyramine will aggravate the diarrhea. 

Ann Jeina was treated with a statin (pravastatin) and cholestyramine, a bile acid sequestrant. With the introduction of the cholesterol absorption blocker ezetimibe, the use of cholestyramine with its high level of gastrointestinal side effects may decline. Ezetimibe reduces the percentage of absorption of free cholesterol present in the lumen of the gut and hence the amount of cholesterol available to the enteroc5de to package into chylomicrons. This, in turn, reduces the amount of cholesterol returning to the liver in chylomicron remnants. The net result is a reduction in the cholesterol pool in hepatocytes. The latter induces the synthesis of an increased number of LDL receptors by the hver cells. As a consequence, the capacity of the liver to increase hepatic uptake of LDL from the circulation leads to a decrease in serum LDL levels. 

The bile acids sequestrants, particularly cholestyramine, can decrease tlie absorption of numerous dru. For tliis reason, tlie bile acid sequestrants should be administered alone and otlier dru given at least 1 hour before or 4 hours after administration of the bile acid sequestrants. There is an increased risk of bleeding when tlie bile acid sequestrants are administered with oral anticoagulants. The dosage of the antico ulant is usually decreased. The bile acid sequestrants may bind with digoxin, tliiazide diuretics, penicillin, propranolol, tetracyclines, folic acid, and tlie thyroid hormone, resulting in decreased effects of th e dru. ... 

Because of their mechanism of action, bile acid sequestrants can potentially bind with and decrease the oral absorption of almost any other drug. Because these anion-exchange resins contain numerous positive charges, they are much more likely to bind to acidic compounds than to basic compounds or nonelectrolytes. This is not an absolute, however, because cholestyramine and colestipol have been reported to decrease the oral absorption of propranolol (a base) and the lipid-soluble vitamins. A, D, E, and K (nonelectrolytes). As a result, the current recommendation is that all other oral medication should be administered at least 1 hour before or 4 hours after cholestyramine and colestipol. Interestingly, this drug interaction has been used in a beneficial manner to treat digitalis overdose and toxicity. 

The bile acid sequestrants, cholestyramine and colestipol, reduce LDL-cholesterol by up to 30% and their use is supported by RCTs [69]. However, they are not well-tolerated chiefly because of gastro intestinal adverse effects. In patients already on multiple drug therapies timing of administration of resins is difficult as they can interfere with the absorption of other drugs. They need to be given at least 1 h before or at least 4 h after other medications. 

Drug interactions The extent to which vitamin D supplementation alters drug effectiveness and toxicity in humans has been systematically reviewed. Bile acid sequestrants and lipase inhibitors were found to inhibit the absorption of vitamin D from the gut. Statins, rifampicin, isoniazid, hydroxychloroquine, antiepileptics, corticosteroids, immimo-suppressive and chemotherapeutic agents, antiretroviral drugs and H2 receptor antagonists interfered with vitamin D metabolism. The interaction between vitamin D and thiazide diuretics could result in hypercalcaetnia. Vitamin D supplementation decreases concentrations of atorvastatin, and could cause hypercalcaetnia in elderly individuals or tixose with compromised renal function or hyperparathyroidism [84 ]. 

The main adverse reactions to the bile acid sequestrants affect the gastrointestinal (GI) tract. They can also interfere with the absorption of other drugs or fat-soluble vitamins. Colesevelam is more selective for bile acids than colestyramine and colestipol and is less likely to interfere with the absorption of other drugs [15]. 

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