Lecture Notes: Drugs Used for Hyperlipidemia

Introduction to Hyperlipidemia

• Definition: Disorder with elevated fat particles (lipids) in blood.
• Risks: Can lead to heart attack and stroke.
• Major Lipids:
  • Cholesterol
  • Triglycerides
  • Phospholipids

Functions of Lipids

• Cholesterol: Needed for bile acid synthesis, steroid hormones, cell membranes.
• Triglycerides: Energy source; composed of glycerol and fatty acids.
• Phospholipids: Key cell membrane component; act as emulsifiers.

Lipid Transport

• Lipoproteins: Transport lipids in blood; consist of cholesterol/triglycerides core and phospholipids/apolipoproteins shell.
• Types:
  • Chylomicrons: From dietary lipids, mainly triglycerides.
  • VLDL: From liver, more cholesterol than chylomicrons.
  • LDL: Transformed from VLDL, delivers cholesterol.
  • HDL: Transports cholesterol back to liver.

Lipoprotein Functions

• LDL ("bad" cholesterol): Delivers cholesterol; high levels lead to atherosclerosis.
• HDL ("good" cholesterol): Removes cholesterol; low levels contribute to atherosclerosis.

Lipid-Lowering Drugs

HMG-CoA Reductase Inhibitors (Statins)

• Mechanism: Inhibit HMG-CoA reductase, reducing cholesterol production.
• Effects: Increase LDL receptors, lower LDL and triglycerides, may increase HDL.
• Examples: Atorvastatin, Fluvastatin, Lovastatin, Pravastatin, Rosuvastatin, Simvastatin.
• Side Effects: Liver toxicity, muscle problems (myopathy, rhabdomyolysis).

Nicotinic Acid (Niacin)

• Mechanism: Inhibits hormone-sensitive lipase in adipose tissue.
• Effects: Decreases VLDL synthesis, increases HDL.
• Side Effects: Flushing, hyperuricemia, gout, liver toxicity.

Fibrates

• Mechanism: Activate PPAR-alpha in liver/adipose tissues.
• Effects: Increase lipoprotein lipase, remove triglycerides, increase HDL.
• Examples: Fenofibrate, Gemfibrozil.
• Side Effects: GI disturbances, myopathy, gallstone risk.

Bile Acid Sequestrants

• Mechanism: Bind bile acids in intestine, preventing reabsorption.
• Effects: Increase LDL receptors, lower circulating LDL.
• Examples: Colesevelam, Colestipol, Cholestyramine.
• Side Effects: GI issues, decreased vitamin absorption, potential drug interactions.

Cholesterol Absorption Inhibitors

• Mechanism: Bind NPC1L1 protein, reducing cholesterol absorption in the intestine.
• Effects: Lower LDL levels.
• Example: Ezetimibe.
• Side Effects: Mild, suitable for patients intolerant to statins.

PCSK9 Inhibitors

• Mechanism: Monoclonal antibodies that inactivate PCSK9, increasing LDL receptor availability.
• Effects: Lower LDL cholesterol.
• Examples: Evolocumab, Alirocumab.
• Side Effects: Injection site reactions, flu-like symptoms, neurocognitive issues.

Omega-3 Fatty Acids

• Mechanism: Inhibit VLDL and triglyceride synthesis in liver.
• Components: DHA and EPA, Icosapent ethyl.
• Side Effects: GI disturbances, fishy aftertaste, potential bleeding risk.

Conclusion

• Summary: Various drugs are available for managing hyperlipidemia, each with specific mechanisms and side effects.
• Note: Importance of understanding individual patient needs and possible side effects when prescribing these medications.