Bile acid binding exchange resins

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. 

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). 

The bile acid-binding agents are large polymeric cationic exchange resins that are insoluble in water. They bind bile acids in the intestinal lumen and prevent their reabsorption. The resin itself is not absorbed. 

The prototype of a bile acid-binding resin is cholestyramine. Cholestyramine is the chloride salt of a basic anion-exchange resin. Its mechanism of action involves exchanging its chloride ion for bile acids in the intestinal lumen. By binding these bile acids, cholestyramine prevents them from being reabsorbed and, hence, they are... 

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. 

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... 

Cholestyramine, like colestipol, binds bile acids, which are removed from the organism in a form bound to the ion-exchange resin. They are used for the same indications. Synonyms of this drug are colibar, quantalan, questran, and others. 

These drugs are basically anion exchange resins that remain in the gut, bind intestinal bile acids, and greatly increase their fecal excretion (mechanism I in Fig. 23.2). 

They are useful only in hyperlipoproteinemias involving elevated levels of LDL i.e. type Ila, lib and V. They are basic ion exchange resins. They are neither digested nor absorbed in the gut. They bind bile acids in intestine and interrupt their entero-hepatic circulation, leading to increased faecal excretion of bile salts and cholesterol. There is increased hepatic conversion of choles-terol to bile acids. More LDL receptors are expressed on liver cells leading to increased clearance of IDL, LDL and indirectly of VLDL. 

Colestipol and colestyramine bind bile sodium and acidic drugs in the intestine. Interference with the absorption of acidic drugs is minimized by the separating doses (the secondary drug should be taken at least 1 hour before or 4-6 hours after the anion exchange resin). 

Colestyramine is an oral anion-exchange resin, which binds bile acids in the intestine. Bile acids are formed from cholesterol in the liver, pass into the gut in the bile and are largely reabsorbed at the terminal ileum. The total bile acid pool is only 3-5 g but, because such enterohepatic recycling takes place 5-10 times a day, on average 20-30 g of bile acid are delivered into the intestine every 24 hours. Bile acids bound to colestyramine are lost in the faeces and the depletion of the bile acid pool stimulates conversion of cholesterol to bile acid the result is a... 

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). 

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. 

Colestyramine is an anion-exchange resin, intended to bind to bile acids within the gut, but it can also bind with some acidic drugs thereby reducing the amount available for absorption. 

Colestyramine is an ion-exchange resin intended to bind with bile acids in the gut, but it can also bind with drugs as well, leading to a reduction in their absorption. This apparently occurs to a limited extent with valproate. 

Bicarbonate has been shown to compete in vitro with bile acids for binding sites on the colestyramine resin. The chloride ions in the colestyramine resin may cause an anion exchange of not only the bile salts, as is the intention, but also bicarbonate in the small bowel. This removal of bicarbonate from the body can predispose to the development of a hyperchloraemic metabolic acidosis and hyperkalaemia. This might be exacerbated by the bicarbonate-losing and hyperkalaemic effects of spironolactone. 

In the 1950s and 1960s anion-exchange resins, such as colestyramine, were developed with the aim of binding bUe acids in the intestine, which originate from cholesterol elimination in the liver, and thus disrupt their enterohepatic circulation. The sequestered bile acids are then excreted with the faecal stools. Since the transport of the bile acids back to the liver can no longer occur, the serum cholesterol level drops. 

C. Binding of Bile Acids to Anion-Exchange Resins... 

A special application of anion exchangers in bile acid work has resulted from the observations that many resins bind bile acids under physiological conditions (neutral pH and aqueous solutions). 

---