Lipid-lowering medications: Fibrates ~Pharmacology~

Summary

Fibrates are lipid-lowering medications that primarily reduce triglyceride levels in the blood by activating PPAR-alpha receptors. They enhance the breakdown of triglycerides into fatty acids and increase HDL synthesis, although they are less effective in lowering cholesterol compared to statins. Fibrates are often used to treat high triglyceride levels, which can lead to conditions like atherosclerosis and pancreatitis. Common side effects include muscle damage and gallstones, especially when combined with statins or bile acid resins. A mnemonic with a fabric loom helps to remember these pharmacological details.

Takeaways

• 💊 Fibrates are lipid-lowering medications, primarily effective at reducing triglycerides in the blood but less effective at lowering cholesterol.
• 🏋️ Triglycerides are a major component of body fat, composed of glycerol and three fatty acids.
• 📦 Triglycerides and cholesterol are transported through the bloodstream in lipoproteins like chylomicrons, VLDL, LDL, and HDL.
• 🧬 Lipoprotein lipase breaks down triglycerides into fatty acids, which cells can use for energy or store for later use.
• 🔄 Fibrates activate the PPAR-alpha receptor, boosting lipoprotein lipase production and enhancing triglyceride breakdown.
• ⚖️ Fibrates increase HDL (good cholesterol) but have a minimal effect on lowering LDL (bad cholesterol).
• 💪 A significant side effect of fibrates is muscle damage (rhabdomyolysis), especially when combined with statins.
• 🪨 Fibrates raise the risk of gallstones, particularly when used with bile acid resins.
• 🧠 Statins are more effective at lowering cholesterol, while fibrates are superior at reducing triglycerides, making them a good combination for mixed dyslipidemia.
• 🧵 A mnemonic for remembering fibrates: a lady making fabrics represents their role in increasing HDL, while side effects like muscle damage and gallstones are symbolized by her husband carrying heavy boxes.

Q & A

What are fibrates and what is their primary function?

Fibrates are a class of lipid-lowering medications, similar to statins and niacin, primarily used to lower triglyceride levels in the blood.

How do triglycerides form and why are they packaged into lipoproteins?

Triglycerides form from fatty acids and glycerol after consumption of fatty foods. They are not water-soluble, so the body packages them into lipoproteins to transport them through the bloodstream.

What is the role of lipoprotein lipase in the metabolism of triglycerides?

Lipoprotein lipase is an enzyme that breaks down triglycerides into fatty acids, which can then be used by cells for energy production or stored for later use.

How do fibrates work to lower triglyceride levels?

Fibrates activate the PPA Alpha receptor, which increases the production of lipoprotein lipase, enhancing the conversion of triglycerides into fatty acids and thus lowering triglyceride levels.

What are the different types of lipoproteins mentioned in the script, and what do they carry?

The script mentions chylomicrons, VLDL, LDL, and HDL. Chylomicrons carry dietary triglycerides and cholesterol, VLDL carries endogenous triglycerides, LDL delivers cholesterol to cells, and HDL picks up excess cholesterol from tissues.

Why are high levels of triglycerides dangerous?

High levels of triglycerides can lead to atherosclerosis, increasing the risk of cardiovascular complications such as strokes and myocardial infarctions, and can also cause acute pancreatitis.

How do fibrates affect cholesterol levels?

Fibrates have a moderate effect on increasing HDL levels and a low effect on lowering LDL levels, meaning they are less effective at controlling cholesterol compared to triglycerides.

What are common side effects of fibrates?

Common side effects of fibrates include gastrointestinal disturbances and rashes. A more serious side effect is the potential for muscle damage leading to rhabdomyolysis.

Why might the combination of fibrates and statins increase the risk of certain side effects?

Both fibrates and statins can cause muscle-related side effects, and when combined, the risk of rhabdomyolysis is increased.

How do fibrates affect the formation of gallstones?

Fibrates decrease the activity of cholesterol 7 Alpha hydroxylase, leading to less conversion of cholesterol into bile acid and more cholesterol in the bile, which promotes gallstone formation.

What is the mnemonic provided in the script to help remember the effects of fibrates?

The mnemonic involves a lady at a loom making fabrics (fibrates), with finished fabrics on the top shelf in a heavy metal box (HDL), and supplies in lighter boxes for VLDL and LDL. The lady's husband represents side effects, with a muscular body for rhabdomyolysis and a giant gallstone for gallstone formation.