Fibrates, also known as fibric acid derivatives, are a class of medications primarily used to treat lipid disorders. They are particularly effective in lowering triglyceride levels and, to a lesser extent, in increasing high-density lipoprotein cholesterol (HDL-C, often referred to as "good" cholesterol). The impact of fibrates on low-density lipoprotein cholesterol (LDL-C, or "bad" cholesterol) is variable and less pronounced.

Mechanism of Action: Fibrates work by activating peroxisome proliferator-activated receptors (PPARs), specifically PPAR-alpha. This activation leads to several metabolic effects:

  • Increase in the oxidation of fatty acids in liver and muscle.
  • Decrease in the production of triglycerides in the liver.
  • Increase in the removal of triglycerides from the blood.
  • Increase in the production of HDL-C.

Commonly Used Fibrates:

  1. Fenofibrate: Used to treat high levels of triglycerides and often prescribed when dietary changes alone have been insufficient.
  2. Gemfibrozil: Another commonly prescribed fibrate, particularly effective in lowering triglycerides and raising HDL-C levels.

Indications:

  • Primarily indicated for hypertriglyceridemia, especially in cases where triglyceride levels are very high and pose a risk for pancreatitis.
  • Sometimes used for mixed hyperlipidemia (high triglycerides and low HDL-C) when statins are not suitable or in addition to statins for additive effects.

Side Effects:

  • Gastrointestinal discomfort, such as nausea and diarrhea.
  • Increased risk of developing gallstones.
  • Potential for muscle-related symptoms, especially when used in combination with statins.
  • Changes in liver enzyme levels, requiring monitoring.

Contraindications:

  • Liver disease, including primary biliary cirrhosis.
  • Severe kidney disease.
  • Pre-existing gallbladder disease.

Drug Interactions:

  • Increased risk of muscle toxicity when used with statins.
  • Interactions with anticoagulants (like warfarin) as fibrates can enhance the effects of anticoagulants.

Clinical Considerations:

  • Regular monitoring of lipid levels, liver function tests, and kidney function is recommended.
  • Fibrates should be used as part of a comprehensive approach to lipid management, including diet, exercise, and other lifestyle modifications.

In summary, fibrates are a valuable tool in managing certain lipid disorders, particularly high triglycerides. Their use should be individualized based on the patient's lipid profile, tolerance, and the presence of other medical conditions.