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32 Cards in this Set
- Front
- Back
What are the therapeutic lifestyle changes for lowering cholesterol?
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-Diet
-Reduction of choleterol and saturated fats -Addition of cholesterol lowering plant stanols/sterols and soluble fiber -Weight reduction for the overweight -Increased physical activity |
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Describe metabolic syndrome
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-Refers to a constellation of consequences of obesity and insulin resistance
-Therapeutic lifestyle changes are particularly important -Patients are at high rist for developing CHD -Diagnosed when at least 3 of the following are present: i. Waist circum >40in(m), >35 inches(f) ii. Triglycerides >150 iii. Low HDL (<40(m),<50(f)) iv. Hypertension (SBP>130, DBP>85) v. Fasting glucose >110 |
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Describe the diet for elevated LDL
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-Saturated fats and cholesterol suppressed LDL receptor activity thus reducing clearance
-Obesity-> increased hepatic secretion of VLDL -The addition of certain plant steroles and of soluble fiber to the diet can reduce LDL -Sat fat <7% -Polyunsat fat <10% -Monounsat fat <20% -Total fat 25-35% -Carbs 50-60% -Fiber 20-30g/d -Protein ~15% -Cholesterol <200mg/d |
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Describe the diet for hypertriglyceridemia
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-Same diet as for elevated LDL
-When due to metabolic syndrome calorie restriction and exercise to achieve ideal weight are very important -Obesity and insulin resistance underlie the metabolic syndrome -Alcohol restriction is part of the dietary restrictions |
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Describe the diet for chylomicronemia
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A low fat diet decreases the production of chylomicrons from dietary triglycerides
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What are the HMG CoA Reductase Inhibitors?
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-Lovastatin
-Simvastatin -Pravastatin -Fluvastatin -Atorvastatin -Rosuvastatin |
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Describe HMG CoA Reductase Inhibitors
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-"Statins"
-The mainstay of LDL-reducing therapy -Inhibit the rate-limiting enzyme of cholesterol biosynthesis and are very effective in reducing LDL levels -Increase HDL levels moderately -Increase synthesis of NO by direct effect on vascular endothelial cells -Diminish intracellular cholesterol levels -LDL receptor activity increases as a result and the clearance of LDL from plasma is enhanced -Safe and well tolerated -Generally excreted through bile -Not for pregnant women/women who plan to become pregnant |
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Who do you use HMG CoA Reductase inhibitors for?
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-Patients with LDL excess resistant to diet therapy
-Patients with hypertriglycerideemia -Not for pregnant women/women who plan to become pregnant |
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Describe the side effects of HMG CoA Reductase Inhibitors
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-Hepatotoxicity manifested by transaminase elevation (dose dep, 1%)
-Acute myositis (dose-dep, <1%) -Rhabodmyolysis -Renal failure Risk of myocitis increased in patients concurrently taking gemfibrozil, cyclosporin A, nicotinic acid, or erythromycin |
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Where are HMG CoA Reductase Inhibitors metabolized? Where do they act?
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-Targets to the liver
-Act at the liver -Undergo extensive first pass hepatic metabolism mediated by organic anion transporter OATP1B1 |
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Describe Pravastatin
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-HMG CoA Reductase Inhibitor
-Hepatic extraction is 46% of absorbed dose -Administered in the active form -Excreted through bile and kidney -Reduces LDL by ~25-35% -Maximal dose is 80mg/d |
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Describe Simvastatin
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-HMG CoA Reductase Inhibitor
-Hepatic extraction is 80% of absorbed dose -Administered as inactive prodrug with a lactone ring -Lactone ring hydrolyzed enzymatically in the liver to produce the acid form which is active -Excreted through bile -Reduces LDL by ~40% -Maximal dose is 80mg/d |
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Describe Lovastatin
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-HMG CoA Reductase Inhibitor
-Administered as inactive prodrug with a lactone ring -Lactone ring hydrolyzed enzymatically in the liver to produce the acid form which is active -Excreted through bile -Teratogenic in rodents -Reduces LDL by ~40% -Maximal dose is 80mg/d |
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Describe Fluvastatin
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-HMG CoA Reductase Inhibitor
-Administered in the active form -Excreted through bile -Reduces LDL by 25-35% -Maximal dose is 80mg/d |
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Describe Atorvastatin
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-HMG CoA Reductase Inhibitor
-Administered in the active form -Excreted through bile -Reduces LDL levels by 55% -Maximal dose is 80mg/d |
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Describe Rosuvastatin
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-HMG CoA Reductase Inhibitor
-Reduces LDL levels by about 56% -Maximal dose is 40mg/d |
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Describe the combination of statins/HMG CoA reductase inhibitors and bile acid sequestrants
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The induction in LDL levels can be more than additive
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Describe Nicotinic Acid
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-For elevated levels of VLDL, IDL, and LDL
-Reduces LDL and VLDL -Increases HDL levels and reduces Lp(a) levels substantially -Long term use causes significant decrease in recurrent myocardial infarction and has beneficial effect on CV mortality and total mortality as well -Assocaited with increased prevalance of a-fib, GI and derm effects |
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Describe the mechanism of Nicotinic Acid
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-Molecular target is a G-protein Couples Receptors (GPR109A)
-Activation of receptors causes reduction of cAMP leading to reduced levels of hormone senstive lipase in apidose tissue -This reduces FFA mobilization from adipose tissue stores -GRP109A helps protect against ketoacidosis -When blocked by nicotinic acid, the reduced mobilization of FFA means diminised delivery to the liver of FFA for VLDL production -This, hepatic synthesis of VLDL is limited -Nicotinic acid inhibits the activity of diglycerol-acyl-transferase-2 - a key enzyme of triglyceride syntehsis |
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Describe the side effects of nicotinic acid
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-Intense cutaneous flushing and pruritis (prostaglandin mediated)
-Can be blocked by aspirin or NSAIDs -Transitory and disappears after the initial weeks of therapy -Dry skin -Nausea -Vomiting -Diarrhea -Elevations of uric acid and blood sugar -May activate peptic ulcer disease -Can sometimes cause hepatitis (dose related, resolves rapidly upon drug cessation) |
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When should nicotinic acid not be used?
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Caution with patients with
-Liver disease -Diabetes mellitus -Gout -May enhance the activity of some drugs such as vasodilating and postueral hypotensive effect of antihypertensive agents |
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In who should you use nicotinic acid?
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Only in high-risk hyperlipoproteinemic patients in whom dietary therapy achieves insufficient lipid lowering
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Describe nicotinic acid therapy
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-Initiated with 100mg 3x/d
-Dose doubles every 4-7 days until maintenance level of 1.5-3g/d is reached -A sustained release prep or an extended release prep may be given at bedtime in doses which gradually increase to 1000-2000mg daily |
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What are the important bile acid sequestrants?
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-Cholestyramine
-Colestipol -Colesevelam |
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Describe the mechanism of bile acid sequestrants
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-Resins that act to reduce total plasma cholesterol and LDL levels by binding intestinal bile acids
-They interrupt the enterohepatic circulation of bile acids -The feed back inhibition of bile acid synthesis is lifted and cholesterol is converted to bile acids within the hepatocyte -This results in a fall in intracellular cholesterol levels which enhances the synthesis of LDL receptors -The clearance of LDL from plasma is accelerated and is due to increased hepatic LDL receptor activity |
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In whom are bile acid sequestrants useful?
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Patients with primary elevation of LDL
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Describe cholestryamine
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-Bile acid sequestrant
-Reduces CHD risk -Dose is 8-16g -Available as powder to mix with food |
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Describe the side effects of cholestryamine
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-GI effects, particularly constipation, nausea, abdominal discomfort, indigestion
-Better tolerated than colestipol -May interfere with absorption of anionic drugs |
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Describe the side effects of colestipol
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-GI effects, particularly constipation, nausea, abdominal discomfort, indigestion
-Not as well tolerated as cholestryamine --May interfere with absorption of anionic drugs |
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In whom are bile acid sequestrants useless?
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Patients with excess levels of chylomicrons, IDL, or VLDL
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Describe colesvelam
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-Bile acid sequestrant
-Causes modest reduction in blood glucose levels in pateints with type II diabetes mellitus -Approved for treatment of diabetes mellitus and reduction of LDL -Available as tablets (usual dosing is 6 tablets/3.75g/d) |
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Describe colestipol
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-Bile acid sequestrant
-Dose is 10-20g -Available as powder to mix with food -Available in tablet form |