Nursing Pharmacology Chapter 11:  Drugs Used in Treating Hyperlipidemia

Hyperlipoproteinemia: Pathophysiology

• Lipoprotein Metabolism: normal

  •  Structure:

    • Lipoprotein core involving cholesteryl esters and triglycerides

    •  Surrounding core: monolayer consisting of:

      • Unesterified cholesterol

      • Phospholipids

    • Surface: occupied by specific proteins (apolipoproteins)

•  Lipoproteins: catabolism and synthesis

  • Chylomicrons:

    • Largest lipoproteins

    • Site of synthesis: intestinal

    • Function: transport dietary triglycerides

  • Very Low Density Lipoproteins (VLDL)

    • Site of synthesis: Liver

    • Function: triglyceride export to peripheral tissue

    • Increased LDL plasma concentration due to:

      • Increased VLDL secretion

      • Decreased LDL catabolism

  •  Low Density Lipoproteins (LDL)

    • Catabolism: receptor-mediated endocytosis {hepatocytes and most other nucleated cells}

    • Other cholesterol source:

      • de novo synthesis:

      • About 50% of LDL removal from plasma: due to LDL endocytosis by hepatocytes

      • Hepatic cholesterol also obtained by endocytosis of VLDL remnants and chylomicron remnants

    • Cholesterol Elimination:hepatocytes

      • Hepatocytes (cholesterol secretion) leads to  bile

      • Hepatocytes cholesterol leads to bile acids leads to  bile

  • Lp(a) Lipoprotein

    • Formation: LDL-like moiety --Lp(a) protein (disulfide bridge link)

    • Clinical Significance: Lp(a) lipoprotein:

      • Lp(a) lipoprotein complex I: found in atherosclerotic plaques

      • Inhibits thrombolysis

  • High-Density lipoproteins (HDL)

    • HDL lipoproteins: liver and intestinal secretion

    • HDL lipid from:

      • Chylomicron surface monolayers and VLDL during lipolysis

      • Cholesterol acquired from peripheral tissues utilizing a pathway protective of cellular cholesterol homeostasis.

1. Primary Reference: Malloy, M. J, and Kane, J. P., Agents Used in Hyperlipidemia, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 563-577.

2. Primary Reference: Ginsberg, H. N and Goldberg, I. J. Disorders of Intermediary Metabolism: Disorders of Lipoprotein Metabolism, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2138-2149.