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    Lipid Lowering Agents

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    DUEÑAS, MARIEL
    This document discusses drugs used to treat dyslipidemia. It begins by defining lipids and lipoproteins, and their roles in transporting lipids between tissues. It then outlines the major classes of lipoproteins and their functions. The document discusses the pathophysiology of atherosclerosis and coronary artery disease. It provides an overview of therapeutic strategies and goals for treating dyslipidemias, including lifestyle changes and drug therapy. The main drug classes for lowering lipids are statins, bile acid sequestrants, niacin, fibrates, ezetimibe, and probucol. Combination drug therapy may be used when single agents are insufficient.

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    Lipid Lowering Agents

    Uploaded by

    DUEÑAS, MARIEL
    53 views56 pages
    This document discusses drugs used to treat dyslipidemia. It begins by defining lipids and lipoproteins, and their roles in transporting lipids between tissues. It then outlines the major classes of lipoproteins and their functions. The document discusses the pathophysiology of atherosclerosis and coronary artery disease. It provides an overview of therapeutic strategies and goals for treating dyslipidemias, including lifestyle changes and drug therapy. The main drug classes for lowering lipids are statins, bile acid sequestrants, niacin, fibrates, ezetimibe, and probucol. Combination drug therapy may be used when single agents are insufficient.

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    This document discusses drugs used to treat dyslipidemia. It begins by defining lipids and lipoproteins, and their roles in transporting lipids between tissues. It then outlines the major classes of lipoproteins and their functions. The document discusses the pathophysiology of atherosclerosis and coronary artery disease. It provides an overview of therapeutic strategies and goals for treating dyslipidemias, including lifestyle changes and drug therapy. The main drug classes for lowering lipids are statins, bile acid sequestrants, niacin, fibrates, ezetimibe, and probucol. Combination drug therapy may be used when single agents are insufficient.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    53 views56 pages

    Lipid Lowering Agents

    Uploaded by

    DUEÑAS, MARIEL
    This document discusses drugs used to treat dyslipidemia. It begins by defining lipids and lipoproteins, and their roles in transporting lipids between tissues. It then outlines the major classes of lipoproteins and their functions. The document discusses the pathophysiology of atherosclerosis and coronary artery disease. It provides an overview of therapeutic strategies and goals for treating dyslipidemias, including lifestyle changes and drug therapy. The main drug classes for lowering lipids are statins, bile acid sequestrants, niacin, fibrates, ezetimibe, and probucol. Combination drug therapy may be used when single agents are insufficient.

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    DRUGS FOR

    DYSLIPIDEMIA
    TOPIC OUTLINE
    1. Lipids
    2. Lipoproteins
    3. Physiology of Handling Lipids
    4. Treatment Goals
    5. Drugs
    LIPIDS

    — Biomolecules that are soluble in organic solvents


    and insoluble in water.
    — Types:
    ¡ Hydrolyzable – can be broken down into simpler
    molecules by hydrolysis through an enzyme (Lipoprotein
    lipase)
    ÷ Triglycerides – upon hydrolysis, yields FFA and
    glycerol
    ¡ Non-hydrolyzable – cannnot be broken down into
    simpler molecules by hydrolysis
    ÷ Cholesterol – a steroid
    Structure of Lipoproteins

    — Triacylglycerols
    — Cholesteryl esters
    — Phospholipids
    — Free cholesterol
    — Apoproteins
    PHYSIOLOGICAL ROLE OF
    PLASMA LIPOPROTEINS

    q T R A N S P O RT L I P I D S B E T W E E N T I S S U E

    Major Groups of Lipoproteins


    1. CHYLOMICRONS
    2. VERY LOW DENSITY LIPOPROTEIN (VLDL)
    3. INTERMEDIATE DENSITY LIPOPROTEIN (IDL)
    4. LOW DENSITY LIPOPROTEIN (LDL)
    5. HIGH DENSITY LIPOPROTEIN (HDL)
    CHYLOMICRONS

    • Largest lipoproteins
    • Primarily triglycerides (80 – 90%)
    • Originate in the intestine from exogenous
    dietary fat
    • Responsible for the transport of dietary
    lipids into circulation
    VERY-LOW-DENSITY LIPOPROTEINS

    — Secreted by liver and export triglycerides to


    peripheral tissues
    — Composed primarily of triglyceride (50 –
    70%) that is derived endogenously from the
    liver
    INTERMEDIATE-DENSITY LIPOPROTEINS

    — Intermediate in the catabolism of VLDL to LDL


    — Remnants of VLDL after the depletion of
    triglycerides
    — Average cholesterol content: 30%
    — Average triglyceride content: 40%
    LOW-DENSITY LIPOPROTEINS

    — Product of intravascular metabolism of the


    triglyceride-rich liproprotein, VLDL.
    — Catabolized chiefly in hepatocytes and other cells
    by receptor-mediated endocytosis
    — Content is primarily cholesterol
    HIGH-DENSITY LIPOPROTEINS

    — Protective lipoproteins
    — Protective effect may result from the
    participation of HDL in reverse cholesterol
    transport
    — Major vehicle for the transport of cholesterol
    from the peripheral tissues to the liver for
    use or excretion
    Exert several antiatherogenic effects:
    1. retrieval of cholesterol from the artery
    wall
    2. inhibit the oxidation of atherogenic
    lipoproteins

    Conveys lipids
    into the artery
    wall
    Cholesterol is waxy fat
    carried through blood by
    lipoproteins

    HDLs (good cholesterol) carry LDLs (bad cholesterol) away from artery walls.
    LDLs stick to artery walls and can lead to plaque build-up (atherocsclerosis)
    What is DYSLIPIDEMIA?

    REFERS TO THE CONDITION OF


    ABNORMAL LIPID LEVELS IN THE
    BLOODSTREAM AND IS A MAJOR RISK
    FACTOR FOR CORONARY HEART
    DISEASE (CHD)
    HYPERLIPIDEMIAS
    — Or Hyperlipoproteinemias
    — Are metabolic disorders that involve elevations in
    any lipoprotein species
    — Hyperlipemia denotes increased levels of
    triglycerides.
    — Classes:
    ¡ Primary – result from a single inherited gene defect
    ¡ Secondary – result of a more generalized metabolic
    disorder
    ATHEROGENESIS
    — The process of forming atheromas,
    plaques in the inner lining of arteries.
    Coronary Artery Disease (CAD)

    — A condition
    correlated with high
    plasma lipid levels of
    cholesterol-and/or
    triacylglycerol-
    containing
    lipoprotein particles
    — Primary Risk
    Factors
    ¡ Hyperlipidemia
    ¡ Hypertension
    ¡ Smoking
    ¡ Overweight
    ¡ Sedentary life-style
    Therapeutic Strategies in Treating
    Secondary Hyperlipidemias
    — Nondrug Therapy:
    ¡ Dietary restriction of cholesterol and
    lipids
    ¡ Dietary restriction of sugar

    ¡ Cessation of smoking

    — Drug Therapy:
    ¡ Antihyperlipidemic drugs
    Therapeutic Goal of
    Antihyperlipidemic Drugs

    — Prevention of MI
    ¡ To decrease production of a lipoprotein
    in the plasma
    ¡ To increase catabolism of a lipoprotein
    in the plasma
    ¡ To increase removal of cholesterol from
    the body
    LIPID-LOWERING
    AGENTS

    HYPOLIPIDEMICS
    1. HMG-COA REDUCTASE
    INHIBITORS
    2. BILE ACID SEQUESTRANTS
    (BILE ACID BINDING
    RESINS)
    3. NIACIN
    4. FIBRIC ACID DERIVATIVES
    5. EZETIMIBE
    6. PROBUCOL
    HMG-CoA REDUCTASE
    INHIBITORS

    LOVASTATIN
    PRAVASTATIN
    SIMVASTATIN
    FLUVASTATIN
    ATORVASTATIN
    ROSUVASTATIN
    Properties of Statins

    — Reduce LDL level (alone or in combination with, or


    resins, niacin, ezetimibe)
    — Should be given at night, if to be given as single
    dose, except atorvastatin and rosuvastatin
    ¡ Cholesterol synthesis occurs primarily at night
    — Absorption in enhanced by food (except
    pravastatin)
    — Rosuvastatin is the most efficacious agent for
    severe hypercholesterolemia
    EFFECTS OF STATINS

    On LIPID LEVELS Clinical applications

    — Reduce cholesterol — First line in the


    synthesis management of
    ¡ Up-regulate low-density hypercholesterolemia
    lipoprotein (LDL)
    — Necessary treatment in
    receptors on hepatocytes
    CAD
    — Modest reduction in
    triglycerides
    — Small increase in HDL
    Side effects and Interactions of
    HMG-CoA Reductase Inhibitors
    — Hepatic dysfunction
    — Muscle pain (Myositis) or worse (Rhabdomyolysis)
    — Drug interaction with CYP Inhibitors
    — SHOULD NOT BE GIVEN to women who are
    pregnant, lactating, or likely to become pregnant
    ¡ Rosuvastatin is FDA Category X
    BILE ACID BINDING RESINS

    CHOLESTYRAMINE
    COLESTIPOL
    COLESEVELAM
    Colesevelam
    Colesevelam
    Clinical Uses of Bile Acid Binding Resins

    — Cholestyramine & Colestipol lower cholesterol and


    LDL
    ¡ Used in treatment of patients with primary
    hypercholesterolemia
    ¡ Add-on treatment for hypercholesterolemia
    — Increase triglycerides, VLDL, and HDL
    ¡ Used in combination with Niacin if used to treat patient with
    LDL elevations in persons with combined hyperlipidemia
    Clinical Uses of Bile Acid Binding Resins

    — Used in relieving pruritus in patients who have


    cholestasis and bile salt accumulation

    — In digitalis toxicity
    ¡ Resins bind with digitalis glycosides except Colesevelam
    Adverse Effects

    — Unpalatability, bloating and constipation


    — Increased serum TG
    — Malabsorption of fat soluble vitamins (ADEK) and
    certain drugs
    ¡ Malabsorption of Vit.K may lead to bleeding
    ¡ Inhibit reabsorption of certain drugs (Warfarin, Digoxin)
    — Steatorrhea
    — Colesevelam is Pregnancy Category B
    NIACIN (Vitamin B3)

    Nicotinic acid - one of the


    two forms of niacin
    Niacin inhibits
    VLDL secretion,
    in turn
    decreasing
    production of
    LDL

    Decreased LDL

    Increased HDL
    Mechanism of Action
    Therapeutic Uses

    — Alternative to fibrates for hypertriglyceridemia


    — Useful in patients with combined hyperlipidemia
    and in those with dysbetalipoproteinemia
    ¡ The most effective agent for increasing HDL

    — Used in Lp(a) hyperlipoproteinemia


    ¡ The only agent that may reduce Lp(a)
    Adverse effects

    — Flushing (harmless)
    ¡ Associated with prostaglandin D2

    ¡ Reduced by taking aspirin half hour earlier than niacin

    ¡ Ibuprofen once daily also mitigates the flush

    — Gastrointestinal disturbances
    ¡ Nausea and abdominal discomfort

    — Palpitations (rare)
    — High doses can cause liver disorders, impair glucose
    tolerance and precipitate gout
    FIBRIC ACID
    DERIVATIVES

    INCLUDE:
    GEMFIBROZIL
    CLOFIBRATE
    FENOFIBRATE
    BEZAFIBRATE
    CIPROFIBRATE
    Mechanisms of Action

    — Inhibit triglyceride synthesis and reduces VLDL


    release into circulation
    — Increase lipoprotein lipase activity, which catabolizes
    VLDL and chylomicron
    — Increase catabolism of triglyceride-rich VLDL,
    thereby lowering serum VLDL
    Mechanism of Action

    — Increase HDL through improved Apo A-I and Apo A-


    II synthesis.
    Mechanism of Action
    PPAR-a

    — Peroxisome proliferator-activated receptor


    — Modulates the expression of several proteins
    ¡ up-regulate LPL, ApoA-1, ApoA-II

    ¡ down-regulate ApoC-III
    Effects are
    mediated by
    PPAR-a

    Hepatic and peripheral effects of fibrates


    Therapeutic Uses

    — In hypertriglyceridemias in which VLDL


    predominate and in dysbetalipoproteinemia
    — May be of benefit in treating the
    hypertriglyceridemia that results from treatment
    with viral protease inhibitors
    ADVERSE EFFECTS

    — Rhabdomyolysis (MYOSITIS) is rare but severe


    — Increase risk of cholesterol gallstones
    — Mild GI symptoms
    Ezetimibe

    — A selective inhibitor of intestinal absorption of


    phytosterols and cholesterol
    — Used in primary hypercholesterolemia
    — Also effective in patients with phytosterolemia
    Adverse effects

    — Myositis is rare
    — Low incidence of hepatic dysfunction
    PROBUCOL

    — Increases LDL degradation and cholesterol excretion


    — Decreases cholesterol, LDL, and HDL
    Combined Drug Therapy

    (1) When VLDL levels are significantly increased


    during treatment of hypercholesterolemia with a
    resin;
    (2) When LDL and VLDL levels are both elevated
    initially;
    (3) When LDL or VLDL levels are not normalized with
    a single agent, or
    (4) When an elevated level of Lp(a) or an HDL
    deficiency coexists with other hyperlipidemias

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