ADVANCES IN PHARMACOLOGY OF DYSLIPIDEMIA
Clinical aspects
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PLAN
lipids characteristic lipids metabolism diseases connected with lipids the classification of dyslipidemic disorders the treatment of hiperlipidemias
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Cholesterol and lipids characteristic
lipid - substance with poor water solubility biologically important lipids:
cholesterol
sterols (composition of hydrocarbon rings) glycerides (composition of hydrocarbon chains)
TG & phospholipids
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Cholesterol and lipids characteristic
assimilated from the diet after digestion transported in the body by incorporating lipids within lipoproteins LIPOPROTEIN = apolipoprotein+free cholesterol+phospholipid+TG +cholesteryl ester
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Cholesterol and lipids characteristic
LIPOPROTEIN:
apolipoprotein - a protein that binds to lipids (Apo A, Apo B, Apo C, Apo E) free cholesterol phospholipid (glycerol, two fatty acids, choline phosphate, an emulsifier like lecithin) trigliceride - an ordinary fat molecule (glycerol and three fatty acids) cholesteryl ester(a compound of cholesterol and a fatty acid)
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Cholesterol and lipids characteristic
LIPOPROTEIN:
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Cholesterol and lipids characteristic
CLASSIFICATION OF LIPOPROTEINS
Chylomicrons Very Low Density Lipoproteins (VLDL) intermediate Density Lipoproteins (IDL) Low Density Lipoproteins (LDL) High Density Lipoproteins (HDL)
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Cholesterol and lipids metabolism
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Cholesterol and lipids metabolism
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Reverse cholesterol transport
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Clinical manifestations of hyperlipidemia
atherosclerosis cardiovascular diseases cardiac infarct cerebral infarct pancreatitis
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Classification of primary hyperlipidemia
predominant hypercholesterolemia: TCh, LDL, HDL predominant hypertriglicerydemia: TG, TCh(n), LDL(n) mixed hyperlipidemia: TG, TCh, LDL
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Clinical signs of hyperlipidemia
predominant hypercholesterolemia: xanthelsama (xanthoma), corneal arcus, extensor digitorum xantomas, Achilles tendon xanthomas, aortic stenosis, pre-patellar xanthomas predominant hypertriglicerydemia: lipaemia retinalis , lipemic blood and plasma, eruptive xanthomas, acute pancreatitis, hepatosplenomegaly mixed hyperlipidemia
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Clinical signs of hyperlipidemia
predominant hypercholesterolemia:
predominant hypertriglicerydemia:
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Causes of secondary hypercholesterolemia
hypothyroidism pregnancy cholestatic liver disese drugs (diuretics, ciclosporin, corticosteroids, androgens) nephrotic syndrome anorexia nervosa porphyria hyperparathyroidism
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Causes of secondary hypertriglyceridemia
diabetes mellitus chronic renal disease abdominal obesity excess alcohol hepatocellular disease drugs (beta-blockers, retinoids, corticosteroids)
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Metabolic syndrome
IDF criteria abdominal obesity M >=94cm; F >=88cm) elevated TG (>150mg/dl) Low HDL (M<40mg/dl; F<50mg/dl) elevated blood pressure (>130/85) elevated glycemia (>=100mg/dl)
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Metabolic syndrome
Increased cardiovascular risk Associated with atherogenic dyslipidemia low HDL high TG mildly elevated LDLs small dense LDLs
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Non-pharmacological treatment and prophylaxis
diet regular physical activity cessation of cigarettes limited alcohol usage
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DRUGS USED IN TREATING DYSLIPIDEMIA
statins fibrates niacin bile acid sequestrants ezetimibe omega-3 acids
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Treatment of hypercholesterolemia * statins * bile acid sequestrants * nicotinic acid * ezetimibe
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Treatment of hypertriglycerydemia * fibrates * statins * nicotinic acid * laropriprant * n-3 fatty acids
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Treatment of low HDL level * nicotinc acid * statins * fibrates
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WHEN TO TREAT HYPERLIPIDEMIA?
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WHEN TO TREAT HYPERLIPIDEMIA?
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WHEN TO TREAT HYPERLIPIDEMIA?
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WHEN TO TREAT HYPERLIPIDEMIA?
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Target lipid levels
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Drug increasing TG
corticosteroids estrogens (esp. taken orally) tamoxifen antihypertensives (betablockers, thiazides) isotretinoin bile acid-binding resins ciclosporin antiretroviral (protease inhibitors) psychotropics (phenothiazine, 2nd generation antipsychotics)
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Monitoring lipids and enzymes in patients on lipid-lowering therapy
Lipids
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Monitoring lipids and enzymes in patients on lipid-lowering therapy
CK
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Monitoring lipids and enzymes in patients on lipid-lowering therapy
Liver and muscles enzymes
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