CLINICAL PHARMACOLOGY 2003 (PART 27)

Correction of blood lipid abnormalities offers scope for a major impact on cardiovascular disease. Drugs play a significant role and have a variety of modes of action. Dietary and lifestyle adjustment are components of overall risk prevention. • Pathophysiology • Primary (inherited) and secondary hyperlipidaemias • Management: risk assessment, secondary and primary prevention, drugs, diet, lifestyle • Drugs used in treatment: statins; fibric acid derivatives; anion-exchange resins; nicotinic acid and derivatives SOME PATHOPHYSIOLOGY The normal function of lipoproteins is to distribute and recycle cholesterol. . | 25 SECTION 5 Hyperlipidaemias SYNOPSIS Correction of blood lipid abnormalities offers scope for a major impact on cardiovascular disease. Drugs play a significant role and have a variety of modes of action. Dietary and lifestyle adjustment are components of overall risk prevention. Pathophysiology Primary inherited and secondary hyperlipidaemias Management risk assessment secondary and primary prevention drugs diet lifestyle Drugs used in treatment statins fibric acid derivatives anion-exchange resins nicotinic acid and derivatives SOME PATHOPHYSIOLOGY The normal function of lipoproteins is to distribute and recycle cholesterol. The pathways of lipid metabolism and transport and their primary inherited disorders appear in Figure and can be summarised thus Cholesterol is absorbed from the intestine and transported to the liver by chylomicron remnants which are taken up by the low-density lipoprotein LDL -receptor-related protein LRP . Cholesterol is then transported to peripheral tissues where for example it is converted to steroid hormones or used to form cell walls and membranes. Hepatic cholesterol enters the circulation as very-low-density lipoprotein VLDL and is metabolised to remnant lipoproteins after lipoprotein lipase removes triglyceride. The remnant lipoproteins are removed by the liver through apolipoprotein E-receptors or LDL-receptors LDL-R or further metabolised to LDL and then removed by peripheral tissues or the liver by LDL-R. The quantity of cholesterol transported from the liver to peripheral tissues greatly exceeds its catabolism there and mechanisms exist to return cholesterol to the liver. Through this reverse transport cholesterol is carried by high-density lipoprotein HDL from peripheral cells to the liver where it is taken up by a process involving hepatic lipase. Cholesterol in the plasma is also recycled to LDL and VLDL by cholesterol-ester transport protein CETP . Cholesterol in the liver is reassembled into lipoproteins or .

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