Recording-2025-02-07T07_06_16.035Z

Statins and Cholesterol Metabolism

Overview of Statins

• Statins lower overall lipid levels in the body.

• Work by inhibiting HMG CoA reductase, a critical enzyme in cholesterol metabolism.

• Important medications that decrease cardiovascular disease complications (e.g., strokes, heart attacks, peripheral vascular disease).

Role of Cholesterol

• Cholesterol is vital for cell structure and function.

• Used in:

  • Cell membrane synthesis.

  • Synthesis of steroid hormones and vitamin D.

  • Formation of bile.

• Sourced from diet and synthesized by the liver.

Lipid Absorption and Transport

• Fats and cholesterol from diet absorbed by the small intestines.

• Lipoproteins created to transport fats and cholesterol, as they are not water-soluble:

  • Chylomicrons:

    • Largest, least dense lipoproteins packed by intestinal cells.

    • Released into lymphatic system, then blood via subclavian vein.

• Liver Synthesis of Cholesterol:

  • Occurs via the mevalonate pathway in smooth endoplasmic reticulum of liver cells.

  • Begins with two acetyl CoA molecules forming acetoacetyl CoA.

  • Acetoacetyl CoA and acetyl CoA combine to form HMG CoA using HMG CoA synthase.

  • HMG CoA is reduced to mevalonate by HMG CoA reductase (rate limiting step).

Types of Lipoproteins

• Very Low-Density Lipoproteins (VLDL):

  • Carries triglycerides and cholesterol from the liver to body.

  • Upon unloading triglycerides, convert to LDL.

• Low-Density Lipoproteins (LDL):

  • Smaller and denser than VLDL.

  • Delivers cholesterol throughout the body.

• High-Density Lipoproteins (HDL):

  • Smallest but densest lipoprotein.

  • Carries excess cholesterol from tissues back to liver.

  • Opposite function of LDL.

Cholesterol Accumulation and Cardiovascular Risk

• Excess LDL leads to cholesterol buildup in tissues, especially endothelial cells lining blood vessels.

• Increased cholesterol forms fatty deposits, risking cardiovascular complications (e.g., strokes, myocardial infarctions).

Mechanism of Action of Statins

• Common statins:

  • Simvastatin, Lovastatin, Pravastatin.

  • More potent newer options: Atorvastatin and Rosuvastatin.

• All statins:

  • Inhibit cholesterol synthesis in the liver.

  • Structurally similar to HMG CoA, preventing substrate binding to HMG CoA reductase.

  • Decrease cholesterol synthesis maximally.

• Increased LDL receptors on hepatic cells enhance cholesterol uptake from blood.

• Results:

  • Decreased LDL levels.

  • Increased HDL levels.

  • Moderate decrease in triglycerides (VLDLs).

Statin Metabolism and Side Effects

• Metabolized by cytochrome P450 enzymes in liver.

• Interactions with medications that affect CYP450 activity should be monitored.

• Common side effects include gastrointestinal issues and rashes.

• Serious side effects:

  • Myalgia (muscle pain).

  • Rhabdomyolysis (muscle breakdown) due to decreased coenzyme Q (essential for ATP production in muscle cells).

• Rare hepatotoxicity, especially in those with liver disease.

• Teratogenic effects; contraindicated in pregnancy.

Mnemonic for Statins

• The video suggests creating a mnemonic to facilitate memory retention regarding statins and their effects.