Medical Pharmacology Chapter 11:  Drugs Used in Treating Hyperlipidemia

Primary Hypercholesterolemia

•  Familial Hypercholesterolemia

  • Familial Hypercholesterolemia

    Attribution: Knowles, J Your Health:  Familial Hypercholesterolemia with Stanfored Cardiologisht Joshua Knowles, MD, Ph.D. https://www.youtube.com/watch?v=Kojxp_SM92E Stanford Health Care YouTube Channel: https://www.youtube.com/channel/UCl_mlar6gQ3z94OLr7YPkbA

  • Autosomal dominant trait

  • Serum cholesterol (heterozygous adults): 260-500 mg;

    • Clinical Manifestations: (heterozygous)

      • Tendinous xanthomatosis

      • Xanthelasmas (eyelids -- soft yellowish spots or plaques; form of xanthomas)

      • Premature coronary atherosclerosis

  • Clinical Manifestations: (homozygous)

    • Coronary vascular disease childhood

    • Serum cholesterol levels > 1000 mg/dL

    • early tuberous and tendinous xanthomatosis

    • Plaque-like, elevated xanthomas of aortic valves, digital webs, buttocks, extremities

  • Mechanism:  familial hypercholesterolemia

    • High-affinity LDL receptor defect

  •  Clinical Management:  familial hypercholesterolemia

    • In heterozygotes: drug regimens can result in normal LDL levels

    • Niacin may be beneficial in patients with no LDL receptor function

     

• Familial Ligand-Defective Apolipoprotein B

  • Clinical consequence:  familial ligand-defective apolipoprotein B

    • Impaired LDL endocytosis leads to moderately severe hypercholesterolemia

    • Tendon xanthomas possible

  • Treatment:  familial ligand-defective apolipoprotein B

    • Probably effective: niacin

    • Variably effective: HMG-CoA reductase inhibitors

• Familial Combined Hyperlipoproteinemia

  • May present with LDL elevation only; or VLDL and LDL elevation

  • Serum cholesterol levels usually less than 350 mg/dL

  • Premature CHD: common

  • Treatment: niacin or reductase inhibitor; alternatively, resin plus niacin

• Lp(a) Hyperlipoproteinemia

  • Associated with increased atherogenesis

  • Niacin may be helpful

•  HDL Deficiency

  • Genetic factors leads to very low HDL serum levels

  • Familial hypoalphalipoproteinemia is a more common HDL disorder

    • HDL cholesterol < 35 mg/dL (semidominant genetic transmission)

    • Premature atherosclerosis (low HDL plasma levels: perhaps only identified risk factor)

    • Treatment:

      1. Avoid or limit other CHD risk factors

      2. Niacin to promote higher LDL levels

  • If hypertriglyceridemia is present, HDL cholesterol levels will be low due to cholesterol ester exchange from HDL leads to triglyceride-rich lipoproteins

    • Hypertriglyceridemia treatment may reduce HDL cholesterol to normal

 Secondary Hyperlipoproteinemia

*adapted from: Table 35-4:Malloy, M. J, and Kane, J. P., Agents Used in Hyperlipidemia, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, p 567.

• Estrogen: small doses may induce a severe hypertriglyceridemia (combining very low estrogen dose with the progestational agent will diminish this effect); if estrogen treatment is required, trans-dermal administration is preferred because hepatic first pass effect is avoided

• Hyperlipidemia associated with chronic nephrotic syndrome: requires treatment (due to  CHD prevalence in this patient population)

  • Drugs of choice: bile acid-binding resin + niacin (vitamin B3)

• Hyperlipidemia associated with cholestasis:

  • Treatment indication: neuropathy associated with xanthomatous neuronal involvement.

    • Plasmapheresis preferred

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.

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.

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