Cholesterol lowering agents

The practical development of plant sterol drugs as cholesterol-lowering agents will depend both on structural features of the sterols themselves and on the form of the administered agent. For example, the unsaturated sterol sitosterol is poorly absorbed in the human intestine, whereas sitostanol, the saturated analog, is almost totally unabsorbable. In addition, there is evidence that plant sterols administered in a soluble, micellar form (see page 261 for a description of micelles) are more effective in blocking cholesterol absorption than plant sterols administered in a solid, crystalline form. 

The cholesterol-lowering agents called statins, such as simvastatin (Zocor) and pravastatin (Pravachol), are among the most widely prescribed drugs in the world. Identify the functional groups in both, and tell how the two substances differ. 

It has been found that the 3-hydroxy-3-methylglutaryl-CoA (HMG CoA) inhibitors statins (atorvastatin, pravastatin, and cerivastatin), widely prescribed cholesterol-lowering agents, are able to inhibit phorbol ester-stimulated superoxide formation in endothelial-intact segments of the rat aorta [64] and suppress angiotensin II-mediated free radical production [65]. Delbose et al. [66] found that statins inhibited NADPH oxidase-catalyzed PMA-induced superoxide production by monocytes. It was suggested that statins can prevent or limit the involvement of superoxide in the development of atherosclerosis. It is important that statin... 

When used as monotherapy, statins are the most potent total and LDL cholesterol-lowering agents and among the best tolerated. Total and LDL cholesterol are reduced in a dose-related fashion by 30% or more when added to dietary therapy. 

The therapeutic class that uniquely exemplifies lactone prodrugs are the statins, i.e., the cholesterol-lowering agents that act by inhibiting 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase (EC 1.1.1.34). This microsomal enzyme catalyzes conversion of HMG-CoA to mevalonate, an important rate-limiting step in cholesterol biosynthesis. Cholesterol synthesis occurs mainly... 

Within a programme aimed at the development of thyroid hormone analogues as potentially useful plasma cholesterol-lowering agents, the pyrida-zinone derivative SK F L-94901 (98) has been prepared and investigated in the U.K. [419-422]. Whereas naturally occurring thyroid hormones cannot be employed for this purpose because of their undesirable effect on heart rate, (98) has been found to represent a potent thyromimetic which retains hepatic activity but lacks cardiac activity. Structural modifications and QSAR studies have been carried out [422]. 

The most important class of cholesterol-lowering agents is the statins. These include lovastatin (Mevacor), simvastatin (Zocor), pravastatin (Pravachol), and atorvastatin (Lipitor), among others. These molecules work, in modest part, by inhibiting biosynthesis of cholesterol and, in larger part, by increasing the rate at which cholesterol is eliminated by the body. Let s have a look at this in more detail. 

Endo A. (1985) Compactin (ML-236B) and related compounds as potential cholesterol-lowering agents that inhibit HMG-CoA reductase. J Med Chem 28 401 05. 

Zaragozic acid or the squalastatins were discovered as fungal metabolites and have been identified as potent inhibitors of squalene synthase. These compounds have presented themselves as potential cholesterol lowering agents. 

It is cholesterol lowering agent with antioxidant property. It is only 1/10 absorbed when given orally. It reduces the serum cholesterol levels without reduction in serum triglycerides level and also reduces the HDL levels. It has no effect on VLDL and triglyceride levels. 

Cyclosporine prolongs the half-life of statin drugs. Therefore, in transplant recipients, the preferred dose of these cholesterol-lowering agents is half of the recommended dose. Some of these agents have been reported to cause rhabdomyolysis when given to patients receiving cyclosporine-A. 

Chinese red rice products include natural HMG CoA reductase inhibitors (primarily lovastatin) and are used as cholesterol-lowering agents. 

Patel SB. Ezetimibe a novel cholesterol-lowering agent that highlights novel physiologic pathways. 

Some of the most exciting natural products discovered in recent years are the cholesterol-lowering agents derived from fungi (see Chapter 45). These drugs inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), an enzyme critical in the biosynthesis of choles-... 

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