Fibrates

Question 1

What are Fibrates? MOA?

Answer 1

• activate the peroxisome proliferator-activated receptor alpha (PPAR-alpha), which leads to HDL synthesis; upregulation of LPL=Lipoprotein Lipase=triglyceride clearance b/c chylomicrons and VLDL broken down into FFA’s, and (chylomicron remant, or LDL, respectively)
• 1) decreased VLDL production (VLDL’s very high in triglycerides)
• 2) increased LPL=lipoprotein lipase activity🡪LPL hydrolyzes triglycerides in chylomicrons and VLDL to release free fatty acids, which are used for energy or taken up by adipocytes🡪decreasing serum [triglycerides];
• 3) inhibtion of cholesterol 7a-hydroxylase, so decreased bile acid production🡪increased risk of cholesterol gallstones (b/c less bile salts in bile to make cholesterol soluble)

**Should be prescribed to any patient with [triglyceride]>500

Ex. Fenofibrate

• Major effect: decrease triglycerides; Minor effects: lower LDL and increase HDL and decrease bile salt production
• Increase risk of cholesterol gallstones, so contraindicated in pt’s with biliary tree issues; myopathy when given with statins