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Antidislipidemic Drugs PowerPoint Presentation

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Published on : Jul 18, 2021 | Views : 2068 | Downloads : 0

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Slide 1-

Antidislipidemic drugs (Summary) © Dr Ivan Lambev, PhD E-mail: itlambev@mail.bg Medical University of Sofia, Faculty of Medicine Department of Pharmacology and Toxicology
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CVD (cardiovascular disease) is the leading cause of death among the adult population in the world. CHD (coronary heart disease) is the main cause of death in patients with CVD. Total plasma cholesterol, high plasma levels of LDL, low levels of HDL are important risk factors for CHD.
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Free cholesterol Phospholipids Triglycerides Cholesterol esthers Apolipoproteins Structure of lipoproteins
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Chylomicrones Very low density lipoproteins (VLDL) Intermediate density lipoproteins (IDL) Low density lipoproteins (LDL) High density lipoproteins (HDL) Classification of lipoproteins according to theirs density
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They are the main protein ingredient of lipoproteins with the follow functions: (1) Facilitate lipid transportation (2) Activate main enzymes in lipid metabolism – lecithin cholesterol acetyltransferase – lipoprotein lipase – liver triglyceride lipase (3) Connect to receptors on the cell surface Apolipoproteins
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After LDL oxidation free radicals and active oxygen species are formed and they activate macrophages.
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Activated macrophages produce inflammatory cytokines (IL-6, TNF alpha), which damage endothelium and initiate atherogenesis.
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Hypertriglyceridemia can predict CHD risk in independent to HDL way.
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Phenotype I IIa IIb III IV V Lipoprotein increased Chylomicrones LDL LDL and VLDL IDL VLDL VLDL and Chylomicrones Atherogenity NO +++ +++ +++ + + Rate Low High High Medium High Low Plasma cholesterol Norma to Norma to Norma to Plasma triglycerides Norma Adapted from Yeshurun D, Gotto AM. Southern Med J 1995; 88 (4): 379–391 Fredrickson classification of dislipidemias (WHO)
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Notes 1. Fredrickson classification does not take in account HDL-C (cholesterol in HDL), whose low plasma level have significant atherogenic role. 2. Homocysteine (norm 5–15 mmol/l) is produced in methionine metabolism. Increased plasma levels of homocysteine is an independent risk factor for the development of atherosclerosis and CVD, even in normal lipid status. High homocysteine plasma levels are reduced by folic acid (vitamin B3), pyridoxine (vitamin B6) and vitamin B12.
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Drugs, inhibiting cholesterol and lipoprotein synthesis Statins Fibrates Nicotinic acids
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 Statins HMG-CoA reductase inhibitors) – p.o. CYP 3A4 substrates Atorvastatin Lovastatin Simvastatin CYP 2C9 substrates Fluvastatin Rosuvastatin CYP450 substrate Pravastatin ARs: CPK, myositis, rabdomyolysis, hepatotoxicity
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 Fibrates – p.o. (inhibit lipolysis in adipocytes) – Ciprofibrate – Clofibrate – Fenofibrate  Nicotinic acid inhibits secretion of VLDL and reduce production of LDL: – Niacin (Vitamin B3)
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II. Drugs enhancing cholesterol and lipid metabolism (ARs: constipation, decreased GI absorption of many other drugs)  Bile acid sequestrants inhibit bile acid enterohepatic recirculation – p.o. : Colestipol, Colestyramine  Phytoproducts (p.o.): Pectin Pectivit C® (pectin/vitamin C)
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III. Drug, inhibiting intestinal cholesterol absorption: Ezetimibe – p.o. IV. Drugs, containing polyunsaturated essential omega-3-fatty acids: Escimo-3® Omacor®
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Control of total serum cholesterol < 5,2 mM 5,2–6,2 mM  6,2 mM Normal levels Bordeline levels High levels Control in 5 years Control in 12 months + diet In CHD or/and risk factors – lipid status analysis, diet and antidislipidemic treatment Control in 6 months with lipid status analysis, diet and antidislipidemic treatment
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BMI >30: >>> saturated fatty acids > >>salt and >>> sugar >>> (or <<<) alcohol <<< fruits and vegetables Smoking Lipid status Stress Diabetes mellitus Metabolic syndrome Sedentary life style 2/3 of the risk Risk factor for CVD Homocysteine >15 mmol/l 
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Metabolic syndrome – high risk for CVD (European Guidelines, 2003) presence of ≥ 3 risk factors: •Waist > 102 cm in men and > 85 cm in women •Triglycerides ≥ 1,7 mmol/l •HDL-cholesterol < 1 mmol/l in men or < 1,3 mmol/l in women •Arterial hypertension > 130/85 mm Hg •Glucose ≥ 6,1 mmol/l Patients with hypertension and concomitant CVD have increased risk for diabetes mellitus. 
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ATP 3’, 5’-AMP cAMP Lipolysis (–) AC PD Cholesterol synthesis Caffeine > 300 mg/d: 5–6 coffee cups daily (+) (+) Hypercholesterolemia
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Patient’s compliance 200 ml/24 h Quantum therapy device  treatment (+ 1 to 2 measure of BP) non-pharmacological treatment physical activity dietary regimen 8–9 h of sleep avoidance of risk factors