Final answer:
Fenofibrate and gemfibrozil work by activating PPARα, which increases fatty acid oxidation and modulates gene expression leading to decreased triglycerides and slightly increased HDL cholesterol levels. They are used in certain hyperlipoproteinemia cases but have significant risks when combined with statins.
Step-by-step explanation:
Fenofibrate and gemfibrozil are both fibrate drugs used primarily to treat hyperlipoproteinemia, especially when triglyceride levels are markedly elevated. The mode of action (MOA) for both drugs is similar; they activate peroxisome proliferator-activated receptor alpha (PPARα), which in turn increases the oxidation of fatty acids in the liver and muscle. Activation of PPARα also results in the modulation of gene expression which leads to increased synthesis of lipoprotein lipase and reduction of apolipoprotein C-III, which collectively reduce triglyceride levels and may slightly increase high-density lipoprotein (HDL) cholesterol levels.
Fenofibrate and gemfibrozil are typically considered when statins are not sufficient alone or in cases where patients have a significant risk due to high triglyceride levels. However, care must be taken when combining these fibrates with statins due to a markedly increased risk of myopathy and rhabdomyolysis. Monitoring blood lipid profiles is essential during treatment.