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Drugs Used in Hyperlipidemia

Drugs Used in Hyperlipidemia. Hyperlipidemia. Hyperlipoproteinemia (cholesterol, Triglyceride, LDL-C , VLDL) Lead to atherosclerosis and Coronary artery disease (CAD). Hyperlipidemia. Endothelial injury. Thrombosis. Atherosclerosis. Smooth muscle cell proliferation.

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Drugs Used in Hyperlipidemia

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  1. Drugs Used in Hyperlipidemia

  2. Hyperlipidemia • Hyperlipoproteinemia (cholesterol, Triglyceride, LDL-C , VLDL) • Lead to atherosclerosis and Coronary artery disease (CAD)

  3. Hyperlipidemia Endothelialinjury Thrombosis Atherosclerosis Smooth muscle cell proliferation Macrophage inflammatory/immunologic mechanism

  4. Atherosclerosis • Atherosclerosis is a disease which characterized by intimal thickening and lipid deposition. Definition

  5. Atherosclerosis

  6. Lipoprotein

  7. Hypolipidemic drugs

  8. Hypolipidemic drugs • Bile Acid Sequestering resins • HMG CoA Reductase Inhibitors • Fibric Acid Derivatives • Nicotinic Acid (Niacin) • Probucol

  9. CE= cholesteryl ester

  10. 1.Bile Acid Sequestering Resins Colestyramine, colestipol Mechanism of action Binds to bile acid in intestine and prevents its transformation into cholesterol

  11. C l i n i c a l u s e s: ** hypercholesterolemia when a statin is contraindicated ** uses unrelated to atherosclerosis, including: pruritus in patients with partial biliary obstruction (bile acids that deposit into the skin is responsible for the pruritus)

  12. A d v e r s e e f f e c t s: GIT symptoms - nauzea, abdominal bloating,نفخ constipation or diarrhea, because resins not absorbed. resins are unappetizing. This can be minimized by suspending them in fruit juice interfere with the absorption of fat-soluble vitamins and drugs (chlorothiazide, digoxin,warfarin) These drugs should be given at last 1 hour before or 4-6 hours after resin

  13. Effect on Lipids • LDL •  20-30% • HDL • 2-8% • TG • 10% (Esp.TG>250mg/dl )

  14. 2. HMG CoA Reductase Inhibitors (Statin) • lovastatin • atorvastatin • pravastatin • simvastatin • Fluvastatin • Rosuvastatin

  15. Mechanism of Statin • Specific competitive inhibitor to HMG CoAReductase Enzyme which is the rate limiting step in cholesterol biosynthesis

  16. The synergism effect of statin and resin

  17. Effect on Lipids • LDL •  25-55% • HDL •  5-10% • TG •  10-20% (triglycerides < 250 mg/dl) • 35-45% (triglycerides > 250 mg/dl)

  18. A d v e r s e e f f e c t s • mild gastrointestinal disturbances • increased plasma activities in liver enzymes • severe myositis (rhabdomyolysis) and angio-oedema (rare)

  19. Clinical Use • Hyperlipidemia • In atherosclerosis

  20. 3. Fibric acid derivatives (fibrates)Clofibrategemfibrozil fenofibratebezafibrate ciprofibrate

  21. Mechanism of action • - - increase the activity of lipoprotein lipase, • hence increasing hydrolysis of triglyceride in chylomicrons and VLDL particles. • reduce hepatic VLDL production and increase hepatic LDLuptake. • Produce a modest decrease in LDL (~ 10%) and increase in HDL (~ 10%). • But, a marked decrease in TGs (~ 30%).

  22. Effect on Lipids • TG 25-40% • HDL 5-15% • LDL 15-20%

  23. Toxicity GI • nausea., vomiting, gall stone Skeletal Muscle • Myopathy, weakness (Esp. with Statins) Liver • Increase aminotransferase Hematologic change • Anemia, leukopenia

  24. Uses: 1st-line defense for: * patients with low HDL and high risk of atheromatous disease (often type 2 diabetic patients) *mixed dyslipidemia(i.e. raised serum TG and CHO) * patients with severe treatment- resistant dyslipidemia(combination with other lipid-lowering drugs). * Indicated in patients with VERY HIGH [TG]s who are at risk for pancreatitis

  25. 4. Niacin • nicotinic acid (vitamin B3) • Water soluble vitamin • Nicotinic acid acts bydecreasingesterification of hepaticTG, and increasing the activity of lipoproteinlipase . • It decreases hepatic TG production and VLDL Secretion (by ~ 30-50%) • modest reduction in LDL and increase in HDL.Nicotinic acid was the 1st lipid-lowering drug to decrease mortality in patients with CAD. • A d v e r s e e f f e c t s: • flushing, palpitations , GIT disturbances. • Currently, nicotinic acid is rarely used.

  26. Fish oil (rich in highly unsaturated fatty acids) • the omega-3 marine TG • - reduce plasma TG but increase CHO (CHO is more strongly associated wih coronary artery disease) • the effects on cardiac morbidity or mortality is unproven • ( although there is epidemiological evidence that eating fish regularly does reduce ischemic heart disease) OtherLIPID-LOWERING DRUGS

  27. Ezetimibe: Inhibitors of Intestinal CHO Absorption: Reduces CHO absorption and decreases LDL with little change in HDL May be synergistic with statins: so good for combination therapy.

  28. Probucol • A potent lipophilic antioxidant

  29. A t h e r o g e n e s i s involves several stages: • endothelial dysfunction with altered PGI2 and NO synthesis • endothelial cells monocyte attachment • bind LDL • oxidatively modified LDL is taken up by macrophages • having taken up oxidised LDL, these macrophages (now foam cells) migrate subendothelially • atheromatous plaque formation • rupture of the plaque

  30. Vessel Lumen Monocyte LDL AdhesionMolecules Endothelium MCP-1 LDL Modified LDL Cytokines Foam Cell Macrophage Intima HDL Promote Cholesterol Efflux HDL Prevent Foam Cell Formation

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