Fibrates

Summary

Fibrates are a class of drugs that include the drug names fenofibrate, bezafibrate, and gemfibrozil. Clinically, fibrates work as lipid lowering drugs used to treat patients with high cholesterol levels.

These drugs work in the body by activating PPAR-alpha, which has several downstream effects. One of these effects is a stimulation of lipoprotein lipase, which then leads to an increase in triglyceride clearance from the bloodstream. The other downstream effect of activating PPAR-alpha is an increase in formation of HDL by the liver.

In lab testing, patients taking fibrates usually experience a raising of HDL levels, a lowering of LDL levels, and a very strong lowering of triglyceride levels.

Side effects of taking fibrates include the development of cholesterol gallstones, which is caused by inhibition of 7-alpha-hydroxylase. In addition, fibrates can cause myopathy. The risk of myopathy is increased when fibrates are taken together with statins.

Key Points

• Fibrates
  • Drug Names
    • Gemfibrozil
    • Fenofibrate
    • Bezafibrate
  • Clinical Use
    • Lipid-lowering agent
      • Lowers cholesterol and lipid levels in the blood
  • Mechanisms
    • Activates PPAR-alpha
      • PPAR-alpha is a nuclear receptor which has a wide array of downstream effects on metabolism
    • Upregulates lipoprotein lipase (LPL)
      • Stimulation of LPL results in increased metabolic breakdown of triglycerides into fatty acids in the liver and muscles
    • Increases triglyceride clearance
      • Fibrates lower circulating triglyceride levels in the blood by both decreasing synthesis in the liver and increasing their metabolic breakdown
    • Induces HDL synthesis
      • This is thought to result by stimulating gene transcription (e.g. apoA-I and apoA-II)
  • Labs
    • ↓ LDL
    • ↑ HDL
    • ↓↓↓ triglycerides
      • Most effective drug for lowering triglycerides, which may work to prevent development of pancreatitis
  • Side Effects
    • Myopathy (myalgia)
      • Increased risk with statin
        • Statins also cause myopathy and taking both drugs together synergistically increases risk
    • Cholesterol gallstones
      • via inhibition of cholesterol 7-alpha-hydroxylase