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ATHEROSCLEROSIS HYPERLIPIDEMIA

بنام خدا. ATHEROSCLEROSIS HYPERLIPIDEMIA. داروها ي موثر بر آترواسکلروز و ه ي پر ل ي پ ي دم ي. Leading Causes of Death Worldwide ( % ). Ischemic Heart Disease 12.4 % Cerebro-Vascular Accident 8.7 Lower Respiratory Infection 8.5

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ATHEROSCLEROSIS HYPERLIPIDEMIA

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  1. بنام خدا ATHEROSCLEROSISHYPERLIPIDEMIA داروهاي موثر بر آترواسکلروز و هيپر ليپيدمي

  2. Leading Causes of Death Worldwide ( % ) • Ischemic Heart Disease 12.4 % • Cerebro-Vascular Accident 8.7 • Lower Respiratory Infection 8.5 • Diarrheal Diseases 5.8 • . . . . .

  3. Risk factors for cardiovascular diseases • Atherosclerosis • Hyperlipidaemia • Obesity, Cigarette smoking, Diabetes • Hypo-activity, Stress, . . .

  4. Risk factors for atherosclerosis • Cholesterol • Obesity, Cigarette smoking, Diabetes • Hypo-activity, Stress, . . .

  5. Dyslipidemia Hyperlipidemia or Hypercholestrolemia منجر به آترواسكلروز ميشود . . . . . . . . . . . . . . . . . . Hyperlipemia منجر به پانكرآتيت ميشود

  6. Hyperlipemia (TG) هيپر تري گليسريدمي از نشانه هاي اصلي ”سندروم متابوليك“ است. علايم ديگر آن عبارتند از: بالا بودن ال-دي-ال و مقاومت به انسولين و بالابودن فشار خون و چاقي شكمي

  7. ATHEROSCLEROSIS

  8. ATHEROSCLEROSIS 1 3 5 4 2 6

  9. Lipoproteins • Makes lipids water soluble (spheres) classified by: • Size, function, content of proteins and • Cholesterol • Triglycerides and phospholipids • High Trig (HYPERLIPEMIA) - Pancreatitis

  10. Lipoproteins Classification: • Main classes: • Chylomicrons • Very low density lipoproteins (VLDL) • Low Density Lipoprotein (LDL) (HCC) • High Density Lipoprotein (HDL) • - - - - - • HCC = High Cholesterol Content

  11. N = 1500 N = 1800

  12. THE LDL RECEPTOR: Low-density Lipoprotein (LDL)

  13. سرنوشت کلسترول (1) 1 - در خون به صورت آزاد وجود ندارد 2 - در خون به صورت بسته بندي شده وجود دارد 3 - اين بسته ها به طرف گيرنده رفته با آن وارد سلول ميشوند 4 - در سلول کلسترول آزاد ميشود 5 - گيرنده دوباره به سطح سلول ميايد 6 - Receptor, Receptor life span, internalilization

  14. سرنوشت کلسترول (2) 1 - منابع کلسترول: خارجي ( غذا ) و داخلي ( سنتز از استات ) 2 - در صورت حذف خارجي سنتز به داد ميرسد 3 - گلوگاه سنتز : Hydroxy Methyl Glutaryl Co-AReductase 4 - وقفه اين آنزيم باعث کشيده شدن و تخليه کلسترول از خون ميشود 5 - براي كشيده شدن بايد گيرنده ساخت كه بغل كند و بياورد تو 6 - محل اين حرف ها کبد است

  15. Cholesterol functions and importance Cell membrane Steroids Bile acids Others

  16. Background (1) Epidemiology: A direct relationship between LDL and cardiovascular diseases

  17. Background (2) History of the LDL receptors 1986 Nobel Prize Winners: M. Brown and J. Goldstein

  18. Ranges Cholesterol: high normal200 mg/dl Dawa Sare 100 mg/dl ? LDL: high normal 160 mg/dl

  19. امروز LDL < 100 mg/ dL حتي هفتاد (70) اگر ريسك فاكتور ها بالا باشد

  20. پس اين دو مهم هستند Cholesterol LDL

  21. Cholesterol SYNTHESIS FATE : Don’t come, LPL, Get out

  22. HMG CoA Reductase Inhibitors: (Lovastatin, Simvastatin, Atorvastatin) Bile Acid-Binding Resins: (Cholestyramine Colestipol ) Niacin:Nicotinic Acid Fibric Acid Derivatives: (Gemfibrozil, Clofibrate, Fenofibrate) Pharmacotherapy of Hyperlipidaemia

  23. Ezetimib (Inhibotor of proteinresponsible for cholesterol transport) Orlistat (Inhibitor of pancreatic lipase) Pharmacotherapy of Hyperlipidaemia

  24. HMG-CoA Reductase Inhibitors • Inhibits rate limiting step in hepatic cholesterol biosynthesis (JAZZABIIAT) •  high- affinity LDL receptors on hepatocyte surface. •  Serum LDL clearance. • Also modest  in plasma TG and small increase in HDL cholesterol

  25. مكانيسم اثر دارو (كه له ور) تو احيا ميكني. پس احيا كن هستي. حالا كه اينطور است: من را احيا كن با تمايل بيشتر. قربانت

  26. اثر دارو - جلوگيري از بيوسنتز كلسترول - تحريك ساختن گيرنده ال-دي-ال - مختصر كاهش تري گليسريد - مختصر افزايش اچ-دي-ال خون

  27. ADR • Liver function enzymes •  Creatine kinase (10% pts) • Myopathy, Muscle weakness, Rhabdomyolysis • Teratogen

  28. Cholesterol functions and importance Cell membrane Steroids Bile acids Others

  29. نبايد داد در:حاملگي و بچه هاي كمتر از 8

  30. Simvastatin Therapeutic Lifestyle Change (TLC) شش هفته اين بالايي بعد دارو ميگويد سيم واستاتين از بقيه بهتر است بسته به تعداد و نمره ريسك فاكتور ها : 10 تا 20 ميليگرم چهار (4) بار در روز: 30 تا 40 در صد پايين ميآورد

  31. Bile Acid-Binding Resins: Colestipol & Cholestyramine • Bind bile acids (cholesterol metabolites) in intestinal lumen and prevents absorption • Resin itself is not absorbed • Only in increased LDL levels لطفا مواظب طعم دارو باشيد

  32. ADR • Flatulence, Constipation, Diarrhea • Heartburn • Malabsorption of vit. K and Folic Acid •  Gallstone formation

  33. Niacin (nicotinic acid) 1 - Water-soluble vitamin (B3) 2 - Effect on LDL is result of Decreased VLDL production in liver Increased clearance of VLDL by serum LPL. 3 - Increases HDL 4 - ADR:skin

  34. Fibric Acid Derivatives • Gemfibrozil, Fenofibrate, Clofibrate • Increase LPL activity (decrease in TG) • Probably HDL and LDL levels. • Well tolerated • ADR: GI, skin

  35. Any other drug ? Cholesterol absorption inhibitors Ezetimibe blocks the intestinal absorption of cholesterol? لباس زير يک جوري ميشود ( بد جوري ) اين براي كلسترول است يا براي كل چربي ها ؟

  36. Any other drug ? Orlistat A LIPOSTATIN derivastive: Natural inhibitor of pancreatic lipase كپسول هاي 60 و 120 ميليگرم

  37. نمك چي؟آيا اميدي هست؟

  38. Drug Combinations • HMG CO-A reductase inhibitor + • Cholestyramine + Niacin ? ? ? استاتين ها يکي از بهترين نتايج را داده اند استاتين ها يکي از بهترين نتايج را داده اند استاتين ها يکي از بهترين نتايج را داده اند

  39. ءشتخق ريالهسن ّشزفخقسRISK FACTORS • Cigarette smocking • Hypertension (more than 140/90 mmHg) • HDL-C less than 40 mg/dL • Family history of premature CHD • Age: Men more than 45, Women 55 yrs • RISK ASSESSMENT (10 YEARS / CHD)

  40. Non Drug Therapy • Diet • Varzesh • No cigar, No risk factors • No obesity

  41. Atherosclerosis • Is it an inflammatory process? Chlamydia pneumoniae TWAR: The use of antibioticsريفامپين يا روکسي ترومايسين IMMUNOLOGIC PROCESS • LDL oxidation : ANTIOXIDANTS: Vit. E (KHEET KARD) Invasive procedures • Non drug therapy

  42. Atherosclerosis • Is it an inflammatory process? Chlamydia pneumoniae TWAR: The use of antibiotics • Hypercholest. Vs Inflammation • Statins Vs Antibiotics

  43. Atherosclerosis: Diagnosis • Is it an inflammatory process? Chlamydia pneumoniae TWAR: • Cholesterol + LDL Vs Antibody • New Eng J Med : ( January 2003 ) • C- reactive protein is more important than cholesterol + LDL

  44. ATHEROSCLEROSISHYPERLIPIDEMIA Futureآينده Inflammation ? vs Surgery or Angioplasty

  45. Guideline (ATP III) Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel IV) Expected date of update release 2012

  46. Summary Payan

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