Bile acid sequestrant acid reabsorption will decrease cholesterol levels, in particular, low-density lipoprotein (commonly known as "bad cholesterol") in blood. Consequently, these drugs have been used for the treatment of hypercholesterolemia and dyslipidemia. Use of these agents as hypolipidemic agents has decreased markedly since the introduction of the statins, which are more efficacious than bile acid sequestrants at lowering LDL. They are occasionally used as an adjunct to the statins as an alternative to the fibrates (another major group of cholesterol-lowering drugs), which are thought to increase the risk of rhabdomyolysis when used with statins. The bile-acid-binding resins can raise triglycerides modestly (about
Discovery and development of statins that the statins exploit and is used to accommodate their hydrophobic moieties. The specificity and the tight binding of statins is due to orientation and bonding interactions that form between the statin and the HMGR enzyme. Polar interactions are formed between the HMG-moiety and residues that are located in the cis loop of the enzyme. These polar interactions are between Ser, Asp, Lys and Lys (Figure 4). The terminal carboxylate of the HMG moiety forms a salt bridge with the cationic Lys of the enzyme. In addition to the polar interaction, Lys participates in a hydrogen bonding network with Glu,