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 derivativesSOME PATHOPHYSIOLOGYThe normal function of lipoproteins is to distribute and recycle cholesterol. ...
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CLINICAL PHARMACOLOGY 2003 (PART 27) 25 Hyperlipidaemias SYNOPSIS membranes. Hepatic cholesterol enters the circulation as very-low-density lipoprotein Correction of blood lipid abnormalities offers (VLDL) and is metabolised to remnant scope for a major impact on cardiovascular lipoproteins after lipoprotein lipase removes disease. Drugs play a significant role and have a triglyceride. The remnant lipoproteins are variety of modes of action. Dietary and lifestyle removed by the liver through apolipoprotein adjustment are components of overall risk E-receptors or LDL-receptors (LDL-R) or further prevention. metabolised to LDL and then removed by • Pathophysiology peripheral tissues or the liver by LDL-R. • Primary (inherited) and secondary The quantity of cholesterol transported from the hyperlipidaemias liver to peripheral tissues greatly exceeds its • Management: risk assessment, secondary and catabolism there and mechanisms exist to return primary prevention, drugs, diet, lifestyle cholesterol to the liver. Through this reverse • Drugs used in treatment: statins; fibric acid transport, cholesterol is carried by high-density derivatives; anion-exchange resins; nicotinic lipoprotein (HDL) from peripheral cells to the acid and derivatives 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).SOME PATHOPHYSIOLOGY Cholesterol in the liver is reassembled intoThe normal function of lipoproteins is to distribute lipoproteins, or secreted in bile then recycled by absorption at the terminal ileum or excreted inand recycle cholesterol. The pathways of lipidmetabolism and transport and their primary the faeces.(inherited) disorders appear in Figure 25.1 and canbe summarised thus:• Cholesterol is absorbed from the intestine and Lipid disorders transported to the liver by chylomicron remnants, which are taken up by the low-density Disorders of lipid metabolism are manifest by elev- lipoprotein (LDL)-receptor-related protein (LRP). ation of the plasma concentrations of the various• Cholesterol is then transported to peripheral lipid and lipoprotein fractions (total and LDL tissues where, for example, it is converted to cholesterol, VLDL, triglycerides, chylomicrons) and steroid hormones or used to form cell walls and they result, predominantly, in cardiovascular disease. 52125 H Y P E R L I PI D A E M I ASFig. 25.1 Pathways of lipid transport. Adapted from Knopp R H 1999 New England Journal of Medicine 341:498-51 I (with permission).This chapter addresses approaches, non-drug as decreased removal, and thus increase of serumwell as drug, to correct abnormal lipid profiles and triglyceride; there is increased hepatic secretiondiminish vascular disease and its consequences. and thus raised plasma concentration of Deposition of cholesterol in the arterial wall is triglyceride-rich VLDL. Patients are at risk ofcentral to the atherosclerotic process. Carriage of recurrent acute pancreatitis when plasmaVLDL, remnant lipoprotein, and LDL to arteries can triglycerides exceed 10 mmol/1, and especiallythus be viewed as potentially atherogenic. In the 20 mmol/1.reverse process, HDL carries cholesterol away from Familial combined hyperlipidemia (FCHL)the arterial wall and can be regarded as protective (common and most important) in which there isagainst atherogenesis. Overproduction of VLDL in ...