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Overview Lipoprotein metabolism Digestive lipid metabolism
Cholesterol balance Drugs affecting cholesterol metabolism
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Statins Inhibit biosynthesis of cholesterol Lower LDL cholesterol
Mechanism: Promote LDL clearance
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Statins LDL Receptor Acetate HMG-CoA Reductase Cholesterol
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Statins LDL Receptor Acetate HMG-CoA Reductase Cholesterol LDL
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Bile Salt Sequestrants
Promote loss of bile salts from the enterohepatic circulation Lower LDL cholesterol Mechanism: Promote LDL clearance
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Bile Salt Sequestrants
Cholesterol Phospholipid
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Bile Salt Sequestrants and the Enterohepatic Circulation
Duodenum Biliary Transport and Storage Jejunum Ileum Fecal Excretion Colon
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Bile Salt Sequestrants
LDL Receptor Cholesterol LDL
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PCSK9 Inhibitors Prevent PCSK9-mediated degradation of LDL receptors
Lower LDL cholesterol Mechanism: Promote LDL clearance
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Liver Cell or other Cell Type
PCSK9 Inhibitors LDL Receptor Liver Cell or other Cell Type X PSCK9
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Liver Cell or other Cell Type
PCSK9 Inhibitors LDL Receptor Liver Cell or other Cell Type LDL
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Cholesterol Absorption Inhibitors
Inhibit absorption of dietary cholesterol Inhibit reabsorption of biliary cholesterol Lower LDL cholesterol Mechanism : Inhibit LDL formation
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Cholesterol Absorption Inhibitors
Plant sterols and stanols Ezetimibe
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Cholesterol Absorption
LYMPH ENTEROCYTE INTESTINAL LUMEN Cholesterol NPC1L1 ACAT Cholesteryl Ester ABCG5/G8
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Cholesterol Absorption Inhibitors
Plant sterols and stanols Ezetimibe
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Plant Sterols and Stanols
Dietary Cholesterol Sterol/Stanol Free Cholesterol
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Plant Sterols and Stanols
Dietary Cholesterol Sterol/Stanol Free Cholesterol
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Plant Sterols and Stanols
LYMPH ENTEROCYTE INTESTINAL LUMEN Cholesterol NPC1L1 ACAT Cholesteryl Ester ABCG5/G8
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Plant Sterols and Stanols
LYMPH ENTEROCYTE INTESTINAL LUMEN Cholesterol NPC1L1 ACAT Cholesteryl Ester ABCG5/G8
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Plant Sterols and Stanols
LYMPH ENTEROCYTE INTESTINAL LUMEN Cholesterol NPC1L1 ACAT Cholesteryl Ester ABCG5/G8
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Cholesterol Absorption Inhibitors
Plant sterols and stanols Ezetimibe
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X Ezetimibe LYMPH ENTEROCYTE INTESTINAL LUMEN Cholesterol Cholesteryl
NPC1L1 ACAT Cholesteryl Ester ABCG5/G8
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X Ezetimibe LYMPH ENTEROCYTE INTESTINAL LUMEN Cholesterol Cholesteryl
NPC1L1 ACAT Cholesteryl Ester ABCG5/G8
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Cholesterol Absorption Inhibitors
LYMPH ENTEROCYTE INTESTINAL LUMEN CM apoB48 Triglyceride Cholesteryl Ester
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Cholesterol Absorption Inhibitors
LYMPH ENTEROCYTE INTESTINAL LUMEN CM apoB48 Triglyceride Cholesteryl Ester
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Cholesterol Absorption Inhibitors
LYMPH ENTEROCYTE INTESTINAL LUMEN CM apoB48 Triglyceride Cholesteryl Ester
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Cholesterol Absorption Inhibitors
LDL apoB100 Liver Duodenum VLDL apoB100 Jejunum Ileum X CM Remnant apoB48 CM apoB48 Colon
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Mipomersen and Lomitapide
Inhibit apoB synthesis (mipomersen) Inhibit MTP activity (lomitapide) Mechanism : Inhibit LDL formation
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Mipomersen and Lomitapide
X X MTP MTP ApoB Triglyceride secretion Hepatic Steatosis
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Niacin Lowers LDL cholesterol by inhibiting VLDL production
Increases HDL cholesterol
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Niacin Inhibits VLDL Production
Presence of Triglycerides MTP MTP ApoB Absence of Triglycerides Degradation of apoB ApoB
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Niacin Promotes Reverse Cholesterol Transport
LCAT Cholesterol HDL3 Phospholipid pre-ß-HDL apoA-I ABCA1 Selective Lipid Uptake Cholesterol LCAT CETP BILE HDL2 SR-BI PERIPHERAL TISSUES LIVER BLOOD
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Fibrates Decrease trigylceride-rich lipoproteins (VLDL) HDL:
Decrease when baseline levels are high Increase when baseline levels are low
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Mechanisms of Fibrate Actions
Increase activity of lipoprotein lipase Decrease hepatic triglyceride production Increase affinity of LDL for the LDL receptor Increased HDL production, due to increase apoA-I synthesis
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Overview Lipoprotein metabolism Digestive lipid metabolism
Cholesterol balance Drugs affecting cholesterol metabolism
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