HMG-CoA reductase inhibitor (statin)

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Contents 1 Discussion 2 Mechanism of Action 3 Available Medications in this Class 4 References

Discussion

Statins are all inhibitors of the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, which is the enzyme responsible for the rate limiting step in hepatic intracellular cholesterol synthesis. ^[1] Clinical and pathological studies show that high plasma levels of total cholesterol (total-C), low density lipoproteins (LDL-C), and apolipoprotein-B (Apo-B) are associated with the build up of intravascular plaques leading to atherosclerosis.^[2] High total-C, LDL-C, and Apo-B associated atherosclerosis increases the risk for the development of cardiovascular disease.^[2] Conversely, increased plasma levels of high density lipoproteins (HDL-C)are associated with a decreased risk for the development of cardiovascular disease.^[2] Atorvastatin lowers plasma cholesterol and lipoproteins, mainly at the hepatic level, by inhibiting HMG-CoA reductase, which in turn increases the number of hepatocelluar LDL receptors on the cell surface.^[1]

Mechanism of Action

Statins are selective, competitive inhibitors of HMG-CoA reductase. HMG-CoA reductase catalyzes the rate limiting step in hepatic intracellular cholesterol synthesis. HMG-CoA reductase converts HMG-CoA to mevalonate in the cholesterol synthesis cascade[1].Inhibition of intrahepatocellular cholesterol synthesis results in the activation of sterol regulatory element binding proteins (SREBPs). SREBPs are transcription factors and are part of a cellular signaling cascade responsible for the regulation of LDL-R (LDL-receptor) gene expression. Once activated, SREBPs are able to diffuse across the nuclear membrane where they bind to sterol response elements (SREs) resulting in up-regulation of the LDL-R gene transcription and increased expression of LDL-receptors in the hepatocellular membrane. The increased expression of LDL-receptors causes increased cellular uptake of LDL molecules effectively lowering the intravascular (blood) circulating LDL concentration.^[1]

Available Medications in this Class

• Atorvastatin
• Cerivastatin - voluntarily withdrawn from U.S. market 8/2001
• Fluvastatin
• Lovastatin
• Pravastatin
• Rosuvastatin
• Simvastatin

Complete Medication Classification List

References

1. ↑ ^{1.0 1.1 1.2} Armstrong, E. J., P. K. Safo, et al. (2005). Pharmacology of Cholesterol and Lipoprotein Metabolism. Eds: Golan DE., et al. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. pgs: 389-69. Baltimore, Lippincott Williams & Wilkins.
2. ↑ ^{2.0 2.1 2.2} Lipitor® (atorvastation calcium) package insert. New York, NY; Parke-Davis; 2006 Dec.