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Lipid Guidelines - Dr. Ajay Kantharia


Published on

Lipids are a heterogenous group of
water –insoluble ( hydrophobic ) organic
molecules. Presentation on how they affect the body and what to do to prevent their effects.

Published in: Health & Medicine, Technology
  • 2-4 gms EPA + DHA Is only in case of elevated triglycerides above 150 mg/ dl. But for the rest of the public it is 1 g/ day. Quoted below -
    'In the US, the American Heart Association (AHA) recommends the general public consume 2 fatty fish per week; while those with documented heart disease should consume 1 gram of long chain omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) per day via diet or supplementation. '
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Lipid Guidelines - Dr. Ajay Kantharia

  1. 1. Consulting Physician & Cardiologist Critical Care Physician HON. PHYSICIAN : Saifee Hospital Sir H. N. Hospital Motiben Dalvi Hospital Lipids Guidelines
  2. 2. <ul><li>The food that we eat is mixture of </li></ul><ul><ul><li>Carbohydrates </li></ul></ul><ul><ul><li>Proteins </li></ul></ul><ul><ul><li>Fats (LIPIDS) </li></ul></ul><ul><ul><li>Fibres </li></ul></ul><ul><ul><li>Vitamins, minerals, etc </li></ul></ul>
  3. 3. LIPIDS <ul><li>Lipids are a heterogenous group of </li></ul><ul><li>water –insoluble ( hydrophobic ) organic </li></ul><ul><li>molecules . </li></ul>
  4. 4. Lipids are <ul><li>Major source of energy </li></ul><ul><li>Other function . </li></ul><ul><li>Fat soluble vitamins have regulatory or coenzyme function. </li></ul><ul><li>Prostaglandin & steroid hormones </li></ul>
  5. 5. An adult ingests about 60-150 gm of lipids / day. 90% is Triglycerides (TG) The remaining 10% is cholesterol , cholesteryl esters , phospholipids and unesterified (free ) fatty acids.
  6. 6. <ul><li>The bowel has limited capacity for the uptake of cholesterol approximately 1500mg/ day, </li></ul><ul><li>but the uptake of the TG is unlimited . </li></ul>
  7. 7. <ul><li>The various lipids are emulsified, </li></ul><ul><li>degraded, mixed by and with various </li></ul><ul><li>digestive juices & enzymes so that it can </li></ul><ul><li>be absorbed. </li></ul><ul><li>The primary site of lipid absorption is the </li></ul><ul><li>brush border membrane of the intestinal </li></ul><ul><li>mucosal cells. </li></ul><ul><li>From the intestinal mucosal cells they are </li></ul><ul><li>transported to the lymph >> thoracic duct into </li></ul><ul><li>the circulation. </li></ul>
  8. 8. LIPID PROFILE <ul><li>Total Cholesterol </li></ul><ul><li>Triglyceride </li></ul><ul><li>High Density Lipoprotein </li></ul><ul><li>Low Density Lipoprotein </li></ul><ul><li>Very Low Density Lipoprotein </li></ul><ul><li>Chylomicrons </li></ul><ul><li>Various Ratios </li></ul>
  9. 9. What is a Lipoprotein? Protein Lipo (Lipid) + Lipoprotein is a macro-molecular complex in blood carrying protected lipids
  10. 10. Why are lipoproteins formed? Cholesterol is insoluble in water To transport it thro’ blood (92% water) it is combined with Protein to make Watersoluble Lipo proteins -Harper’s Biochemistry (2000),p 268 For utilization and storage in tissues,it is converted to water-insoluble Cholesterol ‘Ester’ -Krause’s (2000), Food,Nutrition and Diet Therapy, p 62
  11. 11. Structure of a Lipoprotein
  12. 12. What is a Apolipoprotein? -Harper’s Biochemistry (2000),p 270 Apo = ‘Derived from’ Apolipoprotein is the name given to ‘ Protein’ part of Lipoprotein (ie,Protein derived from Lipoprotein)
  13. 13. APOLIPOPROTEINS <ul><li>Stabilize the Lipoprotein Structure. </li></ul><ul><li>Important regulatory function in LIPOPROTEIN metabolism. </li></ul>
  14. 14. Which Lipoproteins have which Apolipoproteins ? -Harper’s Biochemistry (2000),p 270 Apolipoprotein Lipoprotein Apo A-I/II/IV HDL,Chylo Apo C-I/II/III VLDL,HDL,Chylo Apo D HDL Apo E VLDL,LDL,HDL,Chylo B-100 has the longest amino acidchain(4536) B-48 means 48 % of B 100 Apo B-100 LDL,VLDL,IDL Apo B-48 Chylo
  15. 15. <ul><li>Why is the study of Lipid important ? </li></ul><ul><ul><li>C V D </li></ul></ul>
  16. 16. WHOM TO TEST ? <ul><li>A personal history of CHD, peripheral vascular disease or CVA </li></ul><ul><li>A Family History of CHD or PVD (especially before age 55 years or hyperlipidemia) </li></ul><ul><li>Hypertension </li></ul><ul><li>Diabetes mellitus </li></ul><ul><li>Physical stigmata of hyperlipidermia </li></ul><ul><li>Obesity (BMI > 28) </li></ul><ul><li>Chronic Renal Disease </li></ul><ul><li>Smoking habits </li></ul>
  17. 17. <ul><li>When should we start examining </li></ul><ul><li>Lipid profile ? </li></ul>
  18. 18. <ul><li>Adults > 20years of age & then every 05 years </li></ul><ul><li>Test children with a family history of premature CHD at age 2 years. </li></ul>
  19. 19. Frequency of Testing <ul><li>Every 5 years from age 20 – 25 years to 60-70 years according to overall risk. </li></ul><ul><li>Borderline cases – vary from 1 to 5 years </li></ul><ul><li>For patients on treatment with Diet – Initially every 3 months then every 6 -12 months </li></ul><ul><li>For patients on medication – initially every 6 – 8 weeks then every 3-6 months </li></ul>
  20. 20. Primary Prevention <ul><li>Primary prevention aims to prevent new onset CHD </li></ul>
  21. 21. Primary Prevention and Risk Factor assessment
  22. 22. Categories of Risk Factors <ul><li>Major, independent risk factors </li></ul><ul><li>Life-habit risk factors </li></ul><ul><li>Emerging risk factors </li></ul>
  23. 23. Major Risk Factors (Exclusive of LDL Cholesterol) That Modify LDL Goals <ul><li>Cigarette smoking </li></ul><ul><li>Hypertension (BP  140/90 mmHg or on antihypertensive medication) </li></ul><ul><li>Low HDL cholesterol (<40 mg/dL) † </li></ul><ul><li>Family history of premature CHD </li></ul><ul><ul><li>CHD in male first degree relative <55 years </li></ul></ul><ul><ul><li>CHD in female first degree relative <65 years </li></ul></ul><ul><li>Age (men  45 years; women  55 years) </li></ul>
  24. 24. Life-Habit Risk Factors <ul><li>Obesity (BMI  30) </li></ul><ul><li>Physical inactivity </li></ul><ul><li>Atherogenic diet </li></ul>
  25. 25. Emerging Risk Factors <ul><li>Lipoprotein (a) </li></ul><ul><li>Homocysteine </li></ul><ul><li>Prothrombotic factors </li></ul><ul><li>Proinflammatory factors </li></ul><ul><li>Impaired fasting glucose </li></ul><ul><li>Subclinical atherosclerosis </li></ul>
  26. 26. Diabetes <ul><li>In ATP III, diabetes is regarded as a CHD risk equivalent. </li></ul>
  27. 27. CHD Risk Equivalents <ul><li>Risk for major coronary events equal to that in established CHD </li></ul><ul><li>10-year risk for hard CHD >20% </li></ul>Hard CHD = myocardial infarction + coronary death
  28. 28. CHD Risk Equivalents <ul><li>Other clinical forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease) </li></ul><ul><li>Diabetes </li></ul><ul><li>Multiple risk factors that confer a 10-year risk for CHD >20% </li></ul>
  29. 29. ATP III Lipid and Lipoprotein Classification <ul><li>LDL Cholesterol (mg/dL) </li></ul><ul><li><100 Optimal </li></ul><ul><li>100–129 Near optimal/above optimal </li></ul><ul><li>130–159 Borderline high </li></ul><ul><li>160–189 High </li></ul><ul><li> 190 Very high </li></ul>
  30. 30. ATP III Lipid and Lipoprotein Classification (continued) <ul><li>HDL Cholesterol (mg/dL) </li></ul><ul><li><40 Low </li></ul><ul><li> 60 High </li></ul>
  31. 31. ATP III Lipid and Lipoprotein Classification (continued) <ul><li>Total Cholesterol (mg/dL) </li></ul><ul><li><200 Desirable </li></ul><ul><li>200–239 Borderline high </li></ul><ul><li> 240 High </li></ul>
  32. 34. LDL Cholesterol Goals and Cutpoints for Therapeutic Lifestyle Changes (TLC) and Drug Therapy in Different Risk Categories Risk Category LDL Goal (mg/dL) LDL Level at Which to Initiate Therapeutic Lifestyle Changes (TLC) (mg/dL) LDL Level at Which to Consider Drug Therapy (mg/dL) CHD or CHD Risk Equivalents (10-year risk >20%) <100  100  130 (100–129: drug optional) 2+ Risk Factors (10-year risk  20%) <130  130 10-year risk 10–20%:  130 10-year risk <10%:  160 0–1 Risk Factor <160  160  190 (160–189: LDL-lowering drug optional)
  33. 35. And –the latest As per July 13 th 2004 NCEP ATP III update, high risk patient needs to achieve LDL-C<70 mg/dL Risk LDL goal mg/dL(NCEP ATP III) 1 LDL goal (Recommendations for modifications to footnote ATP III) 2 CHD (10 yr risk>20%) < 100 < 70 2+ RF -10 yr risk 10-20% -10 yr risk < 10% < 130 < 130 < 100 Unchanged 0-1 RF < 160 Unchanged
  34. 37. Therapeutic Lifestyle Changes in LDL-Lowering Therapy <ul><li>Major Features </li></ul><ul><li>TLC Diet </li></ul><ul><ul><li>Reduced intake of cholesterol-raising nutrients </li></ul></ul><ul><ul><ul><li>Saturated fats <7% of total calories </li></ul></ul></ul><ul><ul><ul><li>Dietary cholesterol <200 mg per day </li></ul></ul></ul><ul><ul><li>LDL-lowering therapeutic options </li></ul></ul><ul><ul><ul><li>Plant stanols/sterols (2 g per day) </li></ul></ul></ul><ul><ul><ul><li>Viscous (soluble) fiber (10–25 g per day) </li></ul></ul></ul><ul><li>Weight reduction </li></ul><ul><li>Increased physical activity </li></ul>
  35. 38. Therapeutic Lifestyle Changes Nutrient Composition of TLC Diet <ul><li>Nutrient Recommended Intake </li></ul><ul><li>Saturated fat Less than 7% of total calories </li></ul><ul><li>Polyunsaturated fat Up to 10% of total calories </li></ul><ul><li>Monounsaturated fat Up to 20% of total calories </li></ul><ul><li>Total fat 25–35% of total calories </li></ul><ul><li>Carbohydrate 50–60% of total calories </li></ul><ul><li>Fiber 20–30 grams per day </li></ul><ul><li>Protein Approximately 15% of total calories </li></ul><ul><li>Cholesterol Less than 200 mg/day </li></ul><ul><li>Total calories (energy) Balance energy intake and expenditure to maintain desirable body weight /prevent weight gain </li></ul>
  36. 39. Other Dietary Considerations <ul><li>Limit trans fatty acids </li></ul><ul><li>Proven dietary components to lower cholesterol: </li></ul><ul><ul><li>Plant stanols/sterols (2 g/day) </li></ul></ul><ul><ul><li>Soluble fiber (10-25 g/day) </li></ul></ul><ul><li>Questionable role of alcohol </li></ul>
  37. 40. Exercise <ul><li>Safety </li></ul><ul><li>Aerobic exercise </li></ul><ul><ul><li>> 20 minutes per activity </li></ul></ul><ul><ul><li>At least 3 days per week </li></ul></ul><ul><li>Promotes weight loss and </li></ul><ul><li> HDL </li></ul>
  38. 41. Smoking Cessation <ul><li>Can lower oxidative stress </li></ul><ul><li>Reversal of endothelial dysfunction </li></ul><ul><li> HDL </li></ul>
  39. 42. Weight Loss <ul><li>Increases HDL </li></ul><ul><li>Improves glycemic control </li></ul><ul><li>Reduces blood pressure </li></ul>
  40. 43. <ul><li>DRUG THERAPY </li></ul>
  41. 44. Drug Therapy <ul><li>The 5 most common clinical situations in </li></ul><ul><li>which drug therapy is needed are </li></ul><ul><li>elevated LDL-C; </li></ul><ul><li>high levels of TGs (200 to 500 mg/dL) despite attainment of LDL-C goals; </li></ul><ul><li>low HDL-C; </li></ul><ul><li>diabetic dyslipidemia; and </li></ul><ul><li>very high TGs and/or chylomicronemia syndrome. </li></ul>
  42. 45. Cholesterol-Lowering Drug Therapy <ul><li>HMG CoA Reductase Inhibitors </li></ul><ul><li>Lovastatin </li></ul><ul><li>Pravastatin </li></ul><ul><li>Simvastatin </li></ul><ul><li>Fluvastatin </li></ul><ul><li>Atorvastatin </li></ul><ul><li>Rosuvastatin </li></ul><ul><li>Cholesterol Absorption </li></ul><ul><li>Inhibitors </li></ul><ul><li>Ezetimibe </li></ul><ul><li>Fibrates </li></ul><ul><li>Gemfibrozil </li></ul><ul><li>Micronized Fenofibrate </li></ul><ul><li>Clofibrate </li></ul><ul><li>Bile Acid Sequestrants </li></ul><ul><li>Cholestyramine </li></ul><ul><li>Colestipol </li></ul><ul><li>Colesevelam </li></ul><ul><li>Niacin </li></ul>
  43. 46. Statins <ul><li>Statins are the most potent agents for lowering LDL-C. These agents work by </li></ul><ul><li>competitively inhibiting the rate-limiting step of cholesterol synthesis and </li></ul><ul><li>upregulating LDL receptors in the liver. </li></ul>
  44. 47. HMG CoA Reductase Inhibitors 1.) LDL Uptake Cholesterol 2.) Synthesis HMG CoA Bile Acids Cholesterol HMG CoA Bile Acids
  45. 48. <ul><li>Start with lower dose and increase as needed (according to LDL) </li></ul><ul><ul><li>Pick dose appropriate to LDL-lowering needed </li></ul></ul><ul><li>Doses should be given in the evening or at bedtime (Atorva and Rosuva can be given any time). </li></ul><ul><li>May need to decrease dose occasionally </li></ul><ul><ul><li>Adding potentially interacting drug </li></ul></ul><ul><ul><li>Profound drop in LDL </li></ul></ul>Statins - Dosing
  46. 49. Statin Adverse Effects <ul><li>Major toxicities: </li></ul><ul><li> Hepatic transaminases </li></ul><ul><li>Myalgias </li></ul><ul><li>Rhabdomyolysis </li></ul><ul><li>Selected minor adverse effects: </li></ul><ul><li>Dyspepsia/heartburn </li></ul><ul><li>Headache </li></ul><ul><li>Taste disturbances </li></ul>
  47. 50. Monitoring of Lipid Lowering Therapy <ul><li>Lipid Profiles </li></ul><ul><ul><li>Before initiation and at 6-12 weeks until stable </li></ul></ul><ul><ul><li>Every 6 months thereafter </li></ul></ul><ul><li>Hepatic Transaminases </li></ul><ul><ul><li>Baseline and every 6-12 weeks until stable </li></ul></ul><ul><ul><li>Every 6 months thereafter </li></ul></ul><ul><li>Creatine Kinase (CK) </li></ul><ul><ul><li>Only as needed </li></ul></ul><ul><li>Glucose, Uric Acid </li></ul>
  48. 51. Signs and Symptoms of Myotoxicity <ul><li>Symptoms consist primarily of gradually decreased muscle strength and localized or generalized muscle weakness. </li></ul><ul><li>Symptoms can occur within days or may not occur for years after starting therapy. </li></ul><ul><li>Symptoms involving other organ systems (such as fatigue, shortness of breath, decreased urine output, dark-colored/turbid urine). </li></ul>
  49. 52. Comparative LDL Effects -70 -60 -50 -40 -30 -20 -10 0 10 40 20 80 10 10 20 20 20 20 80 40 40 40 40 1 5 20 Atorvastatin Simvastatin Pravastatin Lovastatin Fluvastatin Rosuvastatin Am J Cardiol 1998;81:582-7. Am J Cardiol 2001;88:504-8. J Int Med Res 2000;28:47-68. Clin Cardiol 2000;23:39-46. 80 80 80
  50. 53. Comparative HDL Effects -4 -2 0 2 4 6 8 10 12 Atorva Simva Prava Lova Rosuva 10 20 40 40 40 40 20 20 20 20 10 10 40 80 80 Adapted from Jones PH et al. Am J Cardiol 2003;92:152–160 & CURVES Study. Am J Cardiol 1998;81:582-7. 10
  51. 54. Comparative TG Effects -35 -30 -25 -20 -15 -10 -5 0 5 10 40 20 80 10 10 20 20 20 20 80 40 40 40 40 Atorvastatin Simvastatin Pravastatin Lovastatin Rosuvaastatin Adapted from Jones PH et al. Am J Cardiol 2003;92:152–160 & CURVES Study. Am J Cardiol 1998;81:582-7. 10
  52. 55. Drug Interactions <ul><li>Pharmacodynamic </li></ul><ul><ul><li>Risk of hepatotoxicity and/or myalgias or myopathy when combined with fibrates or niacin </li></ul></ul><ul><li>Pharmacokinetic </li></ul><ul><ul><li> absorption with bile acid sequestrants </li></ul></ul><ul><ul><li>Inhibition or induction of CYP-based metabolism </li></ul></ul><ul><ul><li>Inhibition of CYP activity </li></ul></ul>
  53. 56. 2 nd Goal <ul><li>2 nd Goal after LDL C is TG control : </li></ul><ul><li>A TG level >150 mg/dL is considered elevated. After correcting LDL- C, </li></ul><ul><li>TG should be less than 150mg%. </li></ul><ul><li>For patients with mildly elevated TG values (150 to 199 mg/dL), Diet and exercise may be adequate. </li></ul>
  54. 57. 2 nd Goal <ul><li>2 nd Goal….. TG </li></ul><ul><ul><ul><ul><ul><li>… ... Non HDL Cholesterol </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Total Chol. = LDL + VLDL + HDL </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Non HDL Chol = </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Total Chol – HDL = LDL + VLDL </li></ul></ul></ul></ul></ul>
  55. 58. Non HDL Cholesterol Goal <ul><li>Non HDL Chol Goal = </li></ul><ul><li>30 mg above LDL Goal </li></ul>
  56. 59. T G <ul><li>Diseases associated with High TG: </li></ul><ul><li>Type 2 diabetes mellitus, </li></ul><ul><li>Chronic renal failure, nephritic syndrome, Hypothyroidism, </li></ul><ul><li>should be looked for and treated. </li></ul>
  57. 60. T G <ul><li>Drugs that elevate TGs, such as </li></ul><ul><li>corticosteroid therapy, </li></ul><ul><li>estrogen therapy, </li></ul><ul><li>retinoid therapy, or </li></ul><ul><li>high doses of beta-blockers, </li></ul><ul><li>should be stopped or substituted </li></ul>
  58. 61. T G <ul><li>Treatment options: </li></ul><ul><li>1. Increasing dose of statin </li></ul><ul><li>2. Add Fibrate (Finofibrate is preferable) </li></ul><ul><li>3. Add Nicotinic acid </li></ul>
  59. 62. Fibrates <ul><li>Mechanism of action </li></ul><ul><ul><li>Inhibition of cholesterol synthesis </li></ul></ul><ul><ul><li>Decreased TG synthesis </li></ul></ul><ul><ul><li>Inhibition of lipolysis in adipose tissue </li></ul></ul><ul><ul><li>Decreased production of VLDL /  clearance </li></ul></ul><ul><ul><li>Increased plasma and hepatic LPL activity </li></ul></ul><ul><li>Effect on lipids </li></ul><ul><ul><li> TC,  LDL,  HDL,  TG </li></ul></ul>
  60. 63. Fibrates - Dosing and Precautions <ul><li>Dosing </li></ul><ul><ul><li>Gemfibrozil: 600mg BID </li></ul></ul><ul><ul><li>Micronized Fenofibrate: 67mg QD;  to 67-201mg QD </li></ul></ul><ul><ul><li>Clofibrate: 2g daily in divided doses </li></ul></ul><ul><li>Adverse effects </li></ul><ul><ul><li>Nausea, diarrhea, cholelithiasis, phototoxicity </li></ul></ul><ul><li>Drug interactions </li></ul><ul><ul><li>Increased risk of hepatotoxicity and/or myalgias with concurrent statins and/or niacin </li></ul></ul><ul><ul><li>Protein binding displacement (e.g., warfarin) </li></ul></ul>
  61. 64. 3 rd Goal <ul><li>Low HDL-C (<40 mg/dL) is considered a tertiary goal </li></ul>
  62. 65. Major causes of Low HDL <ul><li>Heredity (40% to 60%) </li></ul><ul><li>Elevated triglycerides </li></ul><ul><li>Physical inactivity </li></ul><ul><li>Cigarette smoking </li></ul><ul><li>Diets rich in refined carbohydrates & trans – fats </li></ul><ul><li>Certain B.P. medication (diuretics – B blockers) </li></ul>
  63. 66. Life style factors that Raise HDL <ul><li>Physical activity </li></ul><ul><li>Weight loss </li></ul><ul><li>Diet high in mono unsaturated fats eg. Lean meat, Avocado, nuts, olive oil </li></ul><ul><li>Fish oil containing omega – 3 fatty acids </li></ul><ul><li>Smoking cessation </li></ul><ul><li>Small amounts of alcohol </li></ul>
  64. 67. Medication that Raise HDL <ul><li>Niacin </li></ul><ul><li>Statins </li></ul><ul><li>FIbrates </li></ul><ul><li>Estrogen for women </li></ul><ul><li>Alpha blockers </li></ul><ul><li>CETP inhibitor </li></ul><ul><li>HDL mimetic or artificial HDL </li></ul><ul><li>APO A Milano </li></ul>
  65. 68. Common medications that increases levels of HDL and its subclasses Medication HDL HDL2 HDL3 Apo AI Statins +5 to 10% +5 + 30% -5 to +5% -5 to +5% Fibrates +10 to 15% -5% +5 to +30 -5 to +5 Niacin +25 to 50% +50 to 200% -5 to +5% +5 to +30%
  66. 69. HDL <ul><li>Niacin is drug of choice </li></ul><ul><li>It raises blood glucose level, but still can be used in diabetics with good control </li></ul>
  67. 70. Niacin <ul><li>Mechanism of action </li></ul><ul><ul><li>Inhibition of free fatty acid release from adipose tissue </li></ul></ul><ul><ul><li>Inhibition of cAMP accumulation </li></ul></ul><ul><ul><li>Inhibition of VLDL and LDL synthesis </li></ul></ul><ul><ul><li>Increased LPL activity </li></ul></ul><ul><li>Effects on lipids </li></ul><ul><ul><li> TC,  LDL,  HDL,  TG </li></ul></ul><ul><ul><li>Conversion of LDL phenotypic pattern B into pattern A </li></ul></ul><ul><ul><li>Lowers Lp(a) </li></ul></ul>
  68. 71. Niacin - Dosing <ul><li>Immediate release </li></ul><ul><ul><li>100mg TID;  by 100mg TID every week as tolerated </li></ul></ul><ul><ul><li>Goal = 500-1000mg TID </li></ul></ul><ul><li>Sustained release </li></ul><ul><ul><li>375mg QD;  gradually as needed </li></ul></ul><ul><ul><li>Goal = 500-2000mg QD </li></ul></ul>
  69. 72. Niacin - Precautions <ul><li>Adverse effects </li></ul><ul><ul><li>Flushing, pruritis, headache, fatigue (PG-mediated? -- ASA) </li></ul></ul><ul><ul><li>Gastritis, abdominal pain, aggravation of PUD, hepatotoxicity </li></ul></ul><ul><ul><li>Impaired glucose control,  uric acid concentrations </li></ul></ul><ul><li>Drug interactions </li></ul><ul><ul><li>Alcohol:  risk of hepatotoxicity </li></ul></ul><ul><ul><li>Statins, fibrates:  risk of hepatotoxicity and/or myalgias </li></ul></ul><ul><ul><li>Contra-Indication – H/o gout,peptic ulcer ds., liver ds. </li></ul></ul>
  70. 73. Other Drugs <ul><li>Gastrointestinal-active medication such as a bile acid–binding sequestrant (the </li></ul><ul><li>resins cholestyramine and colestipol, or colesevelam, a nonabsorbable polymer) </li></ul><ul><li>Cholesterol-absorption inhibitor (e.g., ezetimibe) </li></ul>
  71. 74. Bile Acid Sequestrants 1.) LDL Uptake Cholesterol 2.) Synthesis HMG CoA Bile Acids Cholesterol HMG CoA Bile Acids Intestines Intestines
  72. 75. Bile Acid Sequestrants <ul><li>Drug Dose Range </li></ul><ul><li>Cholestyramine 4–16 g </li></ul><ul><li>Colestipol 5–20 g </li></ul><ul><li>Colesevelam 2.6–3.8 g </li></ul>
  73. 76. Ezetimibe <ul><li>Ezetimibe is a cholesterol-absorption inhibitor. </li></ul><ul><li>It lowers LDL-C by about 20%, lowers TGs, and raises HDL-C slightly. </li></ul><ul><li>10 mg/day, and it can be taken at any time of the day. </li></ul>
  74. 77. Ezetimibe: A New Cholesterol Absorption Inhibitor <ul><li>First of a new class of drugs with unique mechanism of action </li></ul><ul><ul><li>Targets intestinal absorption of dietary and biliary cholesterol </li></ul></ul><ul><ul><li>Inhibits absorption of dietary and biliary cholesterol </li></ul></ul><ul><ul><li>Reduces plasma LDL-C </li></ul></ul>Adapted from Leitersdorf E Eur Heart J Suppl 2001;3(suppl E):E17-E23; Miettinen TA Int J Clin Pract 2001;55:710-716; Stein E Eur Heart J Suppl 2001;3(suppl E):E11-E16. <ul><li>In co-administration therapy with statins </li></ul><ul><ul><li>Inhibits cholesterol absorption in the intestine and biosynthesis in the liver (dual inhibition) </li></ul></ul><ul><ul><li>Achieves lipid reductions greater than those with statins alone </li></ul></ul>
  75. 78. <ul><li>Is useful as monotherapy for patients intolerant or nonresponsive to statins or enhanced benefits in addition to statins </li></ul><ul><li>Favorable safety and tolerability profile shown in clinical trials </li></ul><ul><ul><li>similar to placebo </li></ul></ul><ul><ul><li>similar to statin alone, in coadministration </li></ul></ul>
  76. 79. Omega 3 fatty acids <ul><li>The AHA recommends 2 to 4 g/day of eicosapentaenoic acid plus docosahexaenoic acid </li></ul>
  77. 80. Herbs/Natural Products <ul><li>Garlic </li></ul><ul><li>Fish Oils </li></ul><ul><li>Red Yeast Rice </li></ul><ul><li>Dietary Fiber </li></ul><ul><li>Oat Bran </li></ul><ul><li>Plant Sterols </li></ul><ul><li>Guggul </li></ul><ul><li>CoEnzyme Q10 </li></ul>