調整血脂08[2]

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調整血脂08[2]

  1. 1. Therapeutics of Cardiovascular Diseases Lipid-Lowering Drugs and Atherosclerosis 2008 George Hsiao Institute of Pharmacology, TMU
  2. 6. <ul><li>Treatment (lipid-lowering drugs): </li></ul><ul><li>HMG CoA reductase inhibitors ( ‘statins’ ) </li></ul><ul><li>Atovastatin, pravastatin, and simvastatin are examples of 3-hydroxy-3methylglutary coenzyme A (HMG CoA ) reductase inhibitors. These drugs have been shown to reduce blood cholesterol by up to 35% in some patients. </li></ul><ul><li>HMG CoA reductase inhibitors can reduce the risk of dying from a coronary events by up to nearly half. </li></ul><ul><li>Mechanism of action : Statins reversibly inhibit the enzyme HMGCoA reductase, which catalyses the rate-limiting step in the synthesis of cholesterol. </li></ul><ul><li>Adverse effects : Reversible myositis (rare); constipation or diarrhea; abdominal pain and flatulence; nausea and headache; fatigue and insomnia; and rash. </li></ul>
  3. 8. <ul><li>Bile-acid-binding resins </li></ul><ul><li>Colestyramine and colestipol have been shown to decrease the rate of mortality from coronary artery disease. </li></ul><ul><li>Mechanism of action: Basic anion exchange resins act by binding bile acids in the intestine, thus preventing their reabsorption and promoting hepatic conversion of cholesterol into bile acids. </li></ul><ul><li>Adverse effects: Side effects include nausea and vomiting, constipation, heartburn, abdominal pain and flatulence, and aggravation of hypertriglyceridaemia. They may interfere with the absorption of fat-soluble vitamins and certain drugs. </li></ul>
  4. 10. <ul><li>Fibrates </li></ul><ul><li>Fibrates include bezafibrate, ciprofibrate, and gemfibrozil. These are broad-spectrum lipid modulating agents that are ineffective in patients with elevated cholesterol but normal triglyceride concentrations. </li></ul><ul><li>Mechanism of action: Fibrates work in several ways……… (Multiple action drug?) </li></ul><ul><li>Adverse effects : Side effects of fibrates include: </li></ul><ul><li>Myositis-like syndrome ( especially if renal function is impaired ). </li></ul><ul><li>Gastrointestinal disturbances. </li></ul><ul><li>Dermatitis, pruritus, rash, and urticaria. </li></ul><ul><li>Impotence. </li></ul><ul><li>Headache, dizziness, blurred vision. </li></ul>
  5. 11. Effects of Fibrates on Lipid Metabolism Peroxisome proliferator activated receptor  (Transcription factor)
  6. 12. <ul><li>Nicotinic acid </li></ul><ul><li>The side effects of nicotinic acid limit its use in the treatment of hyperlipidaemias. Nicotinic acid has been shown to reduce the incidence of coronary artery disease. </li></ul><ul><li>Mechanism of action: It inhibits VLDL and LDL synthesis; it increases HDL-cholesterol. </li></ul><ul><li>Adverse effects : Flushing, dizziness, headache, palpitation, nausea and vomiting, and pruritus. </li></ul>
  7. 13. Effects of Niacin on Lipid Metabolism
  8. 15. <ul><li>Orlistat (Xenical ) </li></ul><ul><li>Patient should be advised to adhere to dietary guidelines; gastrointestinal adverse events may incrase if taken with a diet high in fat (>30% total daily calories from fat). The daily intake of fat should be distributed over three main meals. If taken with any one meal very high in fat, the possibility of gastrointestinal effect increases. Patients should be counseled to take a multivitamin supplement that contains fat-soluble vitamins. </li></ul><ul><li>Mechanism of action: A reversible inhibitor of gastric and pancreatic lipases thus inhibiting absorption of dietary fats by 30% (at doses of 120 mg 3 times/day). </li></ul><ul><li>Adverse reactions: Anxiety, arthritis, back pain, depression, dizziness, dry skin, ear/nose/throat symptoms, fatty/oily stool (20%),fecal incontinence (12%), fecal urgency (30%), flatus with discharge (40%), headache, increased defecation (11%). </li></ul>

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