Mevacor Cholesterol lowering drug

Baycol (cerivastatin, sold as Lipobay in Europe, Bayer) is a statin, a class of cholesterol-lower drugs. Statins are the most prescribed drugs in the United States, with more than 12 million people taking them, and more than 700,000 people in the United States taking cerivastatin. It received marketing approval on June 26, 1997 and was voluntarily removed from the market on August 8, 2001 because of its link to 100 deaths and several injuries from potentially the muscle disease rhabdomyolysis. The other statins — lovas-tatin (Mevacor Merck) pravastatin (Pravachol Bristol-Myers Squibb) simvastatin (Zocor Merck) fluvastatin (Lescol Novartis) atorvastatin (Lipitor Parke-Davis) rosuvastatin... 

A number of cholesterol-lowering drugs (Pravachol, zocor, and mevacor) are prepared by enzymatic processes. Penicillin antibiotics that have been on the market for decades are produced in large quantities by the enzymatic process. 

Statins are a class of cholesterol-lowering drugs that affect serum cholesterol levels by a variety of mechanisms. Examples include Lipitor, Zocor, Pravachol, Lescol, and Mevacor. Recent evidence... 

Again, Merck spent 91.2 million on DTC ads for Zocor in 2000, versus just 58.2 million that Pfizer spent on Lipitor, yet Lipitor led in sales—and this time, Merck had no excuses. It was Merck that had created the whole anticholesterol category in 1987 with Mevacor. But it lost cholesterol. Lipitor blew it away with a lower price and a more potent initial dose. While the higher dose might cause worse side effects, it sure made the drug look more effective in the marketing. 

ITie 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, A well-known example of such a compound is lovastatin, which is also called mevacor (Figure 26.21). These compounds are potent competitive inhibitors K = 1 nM) of HMG-(]oA 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-( oA 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. The development of statins as effective drugs is further described in Chapter 35. 

E. The statin class of drugs—Lipitor (atorvastatin), Mevacor (lovas-tatin), and Zocor (simvastatin)—is used to treat hypercholesterolemia. This class of drugs lowers cholesterol levels by inhibiting the biosynthesis of cholesterol. Specifically, these drugs inhibit the enzyme P-hydroxy-P-methylglutaryl-CoA (HMG-CoA) reductase, which catalyzes the reaction that converts HMG-CoA to mevalonate. This is the rate-limiting step of cholesterol biosynthesis. 

Atorvastatin is one of a widely prescribed class of drugs called statins, which reduce a person s risk of coronary heart disease by lowering the level of cholesterol in their blood. Taken together, the statins—atorvastatin (Lipitor), simvastatin (Zocor), rosuvastatin (Crestor), pravastatin (Pravachol), lovastatin (Mevacor), and several others—are the most widely prescribed drugs in the world, with an estimated 14.6 billion in annual sales. 

We saw in Section 3.15 that statins (Lipitor, Zocor, Mevacor) lower serum cholesterol levels. These drugs are competitive inhibitors for the enzyme that reduces hydroxymethylglutaryl-CoA to mevalonic acid (page 1197). Recall that a competitive inhibitor competes with the substrate for binding at the enzyme s active site (Section 24.7). Decreasing the concentration of mevalonic acid decreases the concentration of isopentenyl pyrophosphate, so the synthesis of aU terpenes, including cholesterol, is decreased. As a consequence of diminished cholesterol synthesis, the liver forms more LDL receptors— the receptors that help clear LDL from the bloodstream. Recall that LDL (low-density lipoprotein) is the so-caUed bad cholesto-ol (Section 3.15). 

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