Nursing Pharmacology Chapter 11:  Drugs Used in Treating Hyperlipidemia

Lipoprotein Disorders

• Overview: lipoprotein disorders

  • Evaluation: Serum lipid measurement following 10-hour fast

  •  CHD risk:

    • Directly proportional to atherogenic lipoproteins concentration

    • Indirectly proportional to HDL levels

    • Triglyceride levels, preferably less than 150 mg/dL

• Primary Hypertriglyceridemia:

  • "Managing Hypertriglyceridemia: Primary Prevention of CAD"

    Attribution: Bhattacharya R Managing Hypertriglyceridemia: Primary Prevention of CAD* https://www.youtube.com/watch?v=i99mLJadj40 Harvard Medical School Continuing Education https://www.youtube.com/@HMSContinuingEd * CAD = Cardiovascular Disease

  • Definition: triglyceride plasma concentration > 90th or 95th percentile for age and gender (as determined following an overnight fast)

  • Isolated plasma triglycerides elevation may be due to increased VLDL or combinations of elevated VLDL and chylomicrons (rarely a result of elevated chylomicrons only)

    •  Eruptive xanthomas may occur in isolated hypertriglyceridemia

      •  Small, orange-red papules (trunk/extremities; triglyceride levels > 1000 mg/dL  chylomicronemia)

        • Eruptive Xanthomas

          Samsuddin "Eruptive xanthomas" http://www.doctorshangout.com/photo/eruptive-xanthomas

    •  at 1000 mg/dL:

      •  Orange-yellow retinal vessels (lipemia retinalis)

      •  Major risk at this plasma triglyceride concentration: pancreatitis

  • Typical plasma triglycerides elevation: caused by increased hepatic VLDL triglyceride synthesis and secretion

    • Regulation of hepatic triglyceride synthesis:

      •   Free fatty acid availability

      •   Hepatic glycogen levels

      •   Balance between insulin and glucagon

    • Conditions associated with hypertriglyceridemia:

      •   Obesity, insulin resistance, alcohol consumption, inactivity, excessive intake of simple sugars and saturated fats.

      •   At VLDL triglyceride levels > 1000 mg/dL, lipoprotein lipases may become saturated

• Familial Hypertriglyceridemia: (severe)

  • Autosomal dominant (For mixed lipemia there are various modes of inheritance)

  • Possible mechanisms: VLDL overproduction and reduced triglyceride-rich lipoprotein catabolism

  • Fasting triglyceride range: 200-750 mg/dL, with increased VLDL triglycerides only

  • Factors that increase VLDL production worsens lipemia (VLDL and chylomicrons which are competing lipoprotein lipase substrates)

  • Most patients: obese

  • Clinical complaints (depending on lipemia severity): eruptive xanthomas, epigastric pain, lipemia retinalis, pancreatitis

  • Treatment: dietary -- alcohol avoidance, reduced fat intake, avoid exogenous estrogen, weight reduction; some patients may benefit from gemfibrozil (Lopid) or niacin (vitamin B3)

• Familial Hypertriglyceridemia: (moderate, endogenous lipemia)

  • Multiple genetic factors

  • Made worse by factors that increased hepatic VLDL secretion (hypertrophic obesity, alcohol, exogenous estrogen intake, diabetes)

  • Treatment: -- indication presence of atherosclerosis (in the patient or in the patient's family)

    • Weight reduction

    • Dietary fat restriction

    • Alcohol avoidance

    • If necessary, gemfibrozil (Lopid) or niacin (vitamin B3)

• Familial Combined Hyperlipoproteinemia:

  • Elevated VLDL and/or LDL

  • Mechanism: 200% increase in hepatic VLDL secretion

  • Increased CHD risk: Drug therapy (niacin or a resin in combination with niacin)

• Familial Lipoprotein Lipase Deficiency:

  • Autosomal recessive (absence/impairment of lipoprotein lipase/lipoprotein lipase cofactor)

  • Dramatic chylomicron accumulation in plasma:

  • Lipemia worsened by estrogens and pregnancy

  • Clinical presentations (beginning in infancy) include:

    •  Pancreatitis

    •  Eruptive xanthomas

    •  Hepatomegaly

    •  Splenomegaly

    •  Bone marrow foam cell infiltration

    •  At triglyceride levels > 1000 mg/dL --lipemia retinalis

• Familial Apoprotein CII Deficiency:

  • Rare autosomal recessive

  • Presentations similar to familial lipoprotein lipase deficiency

• Familial Dysbetalipoproteinemia:

  • Accumulation of chylomicrons and VLDL reminants

  • Low LDL; high serum cholesterol and triglycerides

  • Clinical Presentations:Familial Dysbetalipoproteinemia:

    • Tuberous/tuberoeruptive xanthomas

    • Planar xanthomas:palmar creases

    • Common: obesity and impaired glucose tolerance-- worsening lipemia

    • Peripheral/coronary atherosclerosis

• Treatment: Familial Dysbetalipoproteinemia:

  • Weight reduction

  • Reduced fat, cholesterol, alcohol intake

  • Niacin (vitamin B3) or gemfibrozil (Lopid) may be needed (typically at low doses).

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.