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Flashcards in Prophylaxis of Coronary Heart Disease Deck (21):
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Hyperlipidemia

High levels of lipid in the blood major risk factor. Most patients asymptomatic until cardiovascular disease produces symptoms; may be inherited or acquired. Diets high in saturated fat and lack of exercise contributes, genetics determine ability to metabolize lipids

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Cholestrol

Component of all cell membranes, synthesis of certain hormones and bile salts, deposited in stratum corneum of the skin, comes from dietary sources, manufactured by cells, primarily in the liver

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Plasma lipoproteins

Clases of lipoproteins: six major classes of plasma lipoproteins -- three relevant to coronary atherosclerosis
-Very-low-density lipoproteins (VLDL): triglycerides
-Low-density lipoproteins (LDL): cholestrol, greatest contributor to coronary heart disease (CHD)
-High-density lipoproteins (HDL): cholestrol

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LDL

Transports cholesterol from liver to tissues and organs; used to build plasma membranes and synthesize other steroids. Carries highest amount of cholestrol; known as bad cholestrol. Contributes to plaque deposits and coronary artery disease

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VLDL

Primary carrier of triglycerides in the blood

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HDL

Manufactured in liver and small intestine, reverse cholesterol transport: assists in transport of cholesterol away from body tissues and back to liver. Known as good cholesterol, transports cholesterol for destruction and removal from body

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Treatment of High LDL Cholesterol

Therapeutic lifestyle changes (TLCs)
-Smoking cessation
-The TLC diet
-Exercise

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Why should drug therapy not be first-line?

Drugs should only be used if TLCs fail
-HMG CoA reductase inhibitors aka statins
-Bile-acids sequestrants
-Nicotinic acid (niacin)

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Secondary treatment targets

Metabolic syndrome: high blood glucose, high triglycerides, high apolipoprotein B, low high-density lipoprotein (HDL), small LDL particles, prothrombotic state, proinflammatory state, hypertension; high triglycerides: levels above 150 mg/dL

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Treatment goals for metabolic syndrome

Reduce the risk for atherosclerotic disease, reduce the risk for type 2 diabetes, increase physical activity

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HMG CoA Reductase Inhibitors (Statins)

Prototype drug: atorvastatin (Lipitor)
Mechanism of action: inhibits HMG-CoA reductase
Primary use: reduce serum-lipid levels
Adverse effects: headache, fatigue, muscle or joint pain, and heartburn, rarely rhabdomyolisis

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HMG-CoA Reductase Inhibitors (Statins)

Most effective drugs for lowering LDL, reduction of LDL cholesterol, elevation of HDL cholesterol, reduction of triglyceride levels, nonlipid beneficial cardiovascular actions: promote plaque stability, reduce risk for cardiovascular events, increased bone formation

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HMG CoA Reductase Inhibitors (Statins): Therapeutic uses

Hypercholesterolemia, primary and secondary prevention of CV events, post-MI therapy, diabetes, potential uses

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HMG CoA Reductase Inhibitors (Statins): Adverse effects

Common: headache, rash, GI disturbances; rare: myopathy/rhabdomyolysis, hepatotoxicity

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HMG CoA Reductase Inhibitor (Statins): Drug Interactions

Most other lipid-lowering drugs (except bile acid sequestrants); drugs that inhibit CYP3A4, use in pregnancy
-Dosing should be once daily in the evening
-Endogenous cholesterol synthesis increases during the night; statins have greatest impact when given in the evening

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Nicotinic Acid (Niacin)

Prototype drug: Niacin
Mechanism of action: to decrease VLDL levels
Primary use: to reduce triglycerides; increase HDL levels
Adverse effects: flushing, hot flashes, nausea, excess gas, diarrhea, hepatotoxicity and gout possible

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Bile-Acid Resins

Prototype drug: cholestyramine (questran)
Mechanism of action: binds with bile acids increasing cholesterol excretion in the stool
Primary use: lower serum-lipid levels
Adverse effects: GI tract, such as bloating and constipation
Able to bind to other drugs, increasing potential for drug interaction

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Bile-Acid Sequestrants

Previously were first-line drugs, now primarily used as adjuncts to statins; Cholestyramine, colestipol, colesevelam: newest and better-tolerated drug, does not decrease uptake of fat-soluble vitamins (as other bile sequestrants do), does not significantly reduce the absorption of statins, warfarin, digoxin, and most other drugs studied

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Bile-Acid Sequestrants: Colesevelam

Reduction in LDL cholestrol, increased VLDL levels in some patients
Mechanism of action: increases LDL receptors on hepatocytes, prevents reabsorption of bile acids
Therapeutic use: reduces LDL cholesterol (in conjunction with modified diet and exercise)
Adverse effects: constipation

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Fibric Acid Derivatives (Fibrates)

Most effective drugs available for lowering TG levels, can raise HDL cholesterol. Little or no effect on LDL cholesterol, can increase the risk for bleeding in patients on warfarin; can increase risk for rhabdomyolysis in patients taking statins. Three drugs in US: gemfibrozil (lopid), fenofibrate (tricor), fenofibric acid (trilipix)

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Gefibrozil

Effects on plasma lipoproteins: decreases plasma TG content, lowers VLDL levels, can raise HDL cholesterol
Mechanism: appears to interact with a specific receptor subtype (PPAR alpha)
Drug interaction: displaces warfarin from plasma albumin, measure INR frequently