Vytorin
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Vytorin (ezetimibe & simvastatin)Vytorin (ezetimibe & simvastatin)
Vytorin is a brand name drug used to treat Dyslipidemia, an abnormal amount of cholesterol or other lipids in the blood. It is composed of two separate medications, Simvastatin (generic for Zocor) and Ezetimibe (generic for Zetia). Ezetimibe works by decreasing cholesterol absorption in the small intestine. The second component of Vytorin, Simvastatin, works by reducing the production of cholesterol.
PharmacodynamicsPharmacodynamics
Ezetimibe
Ezetimibe works to selectively inhibit cholesterol and phytosterol absorption in the body’s intestines. This drug appears to work at the brush border of the small intestine inhibiting cholesterol absorption which then leads to a decrease in cholesterol delivery to the liver. This is different from other cholesterol-reducing compounds because it does not directly inhibit cholesterol synthesis in the liver.[1] By inhibiting the absorption of cholesterol, ezetimibe decreases the cholesterol levels in the blood. [2]. Ezetimibe specifically targets the sterol transporter, which controls cholesterol uptake at the jejunal enterocyte brush border.
Simvastatin
Simvastatin interferes in the production of cholesterol.
Mechanism of ActionMechanism of Action
Ezetimibe
When administered, the drug is inactive until it is absorbed. Upon absorption ezetimibe is conjugated to active phenolic glucuronide where it is metabolized within the small intestine and liver. [3] Ezetimibe limits the internalization of cholesterol by the small intestine. Cholesterol is absorbed into cells with NPC1L1 through clathrin/AP2-mediated endocytosis. AP2 is a multimeric protein that works on the cell membrane to facilitate endocytosis. Ezetimibe inhibits the absorption of cholesterol by blocking the internalization of NPC1L1. [4]
Simvastatin
When the drug is administered it is initially inactive. It must be hydrolyzed in order to become active. Once hydrolyzed, simvastatin reduces the amount of mevalonic acid in the blood by competing for HMG-CoA reductase with HMG-CoA. To produce cholesterol, Acetyl CoA is converted into HMG-CoA, which is then converted into mevalonate. Mevalonate is then converted into isopentenyl pyrophosphate (IPP), IPP is converted into squalene, and then finally squalene is converted into cholesterol. Simvastatin reduces the conversion of HMG-CoA to mevalonate, therefore lowering cholesterol levels. Simvastatin targets which is the enzyme responsible for said conversion. With the synthesis of cholesterol being divided into 5 major steps, this inability to convert targets only the second step in cholesterol synthesis.