Atorvastatinmini
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| Atorvastatin mini monograph a TORE va sta tin (.wav file) |
Authored by: WilliamJ4 09:40, 25 January 2007 (PST) |
| Trade Name(s) | Lipitor (US, UK) |
| How Supplied | Tablets: 10 mg, 20 mg, 40 mg, 80 mg |
| Classification | HMG-CoA reductase inhibitor |
| Pregnancy Category | X |
| Schedule | Rx |
| Description | Atorvastatin belongs to a class of medications known as the statins. 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. 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. High total-C, LDL-C, and Apo-B associated atherosclerosis increases the risk for the development of cardiovascular disease. Conversely, increased plasma levels of high density lipoproteins (HDL-C) are associated with a decreased risk for the development of cardiovascular disease. Atorvastatin lowers plasma cholesterol and lipoproteins, mainly at the hepatic level, by inhibiting HMG-CoA reductase, which in turn increases the number of hepatocellular LDL receptors on the cell surface.[1][2]
Atorvastatin is used to lower cholesterol and triglycerides in patients with hypercholesterolemia and/or mixed dyslipidemia, as well as homozygous familial hypercholesterolemia. The goal of reducing circulating cholesterol (mainly LDL-C) is for the primary and/or secondary prevention of cardiovascular diseases (CVD) such as coronary artery disease (CAD), acute myocardial infarction (AMI), and ischemic cerebrovascular attacks (stroke). Atorvastatin decreases LDL-C by a mean of 39, 43, 50, and 60% for daily doses of 10, 20, 40, and 80 mg, respectively. Furthermore, atorvastatin decreases triglycerides by a mean of 29, 33, 37, 45% for daily doses of 10, 20, 40, and 80 mg, respectively. Atorvastatin increases HDL-C by a mean of 6, 9, 6, and 5% for daily doses of 10, 20, 40, and 80 mg, respectively. Atorvastatin has also shown efficacy in lowering plasma LDL-C levels in patients with homozygous familial hypercholesterolemia (FH), who typically do not respond to lipid lowering therapy.[1] |
| Mechanism of Action | Atorvastatin, like all statins, is a selective, competitive inhibitor 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. 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-receptor (LDL-R) 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-Rs in the hepatocellular membrane. The increased expression of LDL-Rs causes increased cellular uptake of LDL molecules effectively lowering the intravascular (blood) circulating LDL concentration.[1][2] |
| Recent News | No recent news. |
| FDA-approved Indications | FDA-approved indications include:
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References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Lipitor® (atorvastatin calcium) package insert. New York, NY; Parke-Davis; 2006 Dec.
- ↑ 2.0 2.1 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.
- ↑ Andrews TC, Ballantyne CM, Hsia JA, Kramer JH. Achieving and maintaining National Cholesterol Education Program low-density lipoprotein cholesterol goals with five statins. Am J Med 2001;111(3):185-91.
