2. Hyperlipidemia

3. Hyperlipidemia and hyperlipoproteinemia are general terms for elevated concentrations of lipids and lipoproteins in the blood. hypercholesterolemia and hypertriglyceridemia refer specifically to elevated concentrations of cholesterol and triglycerides, respectively. Hypercholesterolemia contributes to the pathogenesis of atherosclerosis, coronary artery. Hypertriglyceridemia is associated with pancreatitis and have role in the development of atherosclerosis and heart disease in some patients.

4. Lipoproteins and Lipid Transport: Because lipids are insoluble in plasma, they must be transported in the circulation in the form of lipoproteins. There are many types of lipoproteins; chylomicrons, very low density lipoproteins (VLDL), low-density lipoproteins (LDL), intermediate-density lipoproteins (IDL), high-density lipoproteins (HDL), and lipoprotein (a). The various types are distinguished in terms of their density, lipid and protein composition, and role in lipid transport.

7. Management of Hyperlipidemia: Modifications of diet: Dietary modifications are the cornerstone of treatment for hyperlipidemia and may be effective by themselves in patients with mildly elevated cholesterol or triglycerides. The diet of patients with hypercholesterolemia should be low in cholesterol, saturated fat, and calories. In some patients with hypertriglyceridemia, supplementing the diet with fish oils that contain omega-3 fatty acids may be useful in lowering the triglyceride levels.

8. Classification of drugs for hyperlipidemia I- Drugs for hypercholesterolemia 1- HMG-CoA reductase inhibitors: Atorvastatin – Lovastatin. 2- Bile acid-binding resins: Cholestyramine – Colestipol. II- Drugs for hypercholesterolemia and hypertriglyceridemia a- Fibric acid derivatives: Bezafibrate - Fenofibrate. b- Miscellaneous drugs and natural compounds - Niacin, Nicotinic acid - Vitamin E and other antioxidants - Probucol - Estrogens

9. HMG-CoA Reductase Inhibitors They are structurally related to 3-hydroxy-3-methylglutaryl-coenzyme A which is converted by HMG-CoA reductase to mevalonic acid, reducing hepatic cholesterol biosynthesis. This increases the number of hepatic LDL receptors and enables more LDL to be delivered to the liver. As a result, there is a reduction in the level of LDL cholesterol in the serum. They also reduce serum triglycerides. The HMG-CoA reductase inhibitors are used for the treatment of hypercholesterolemia. They are relatively free of adverse effects, but they may elevate hepatic enzymes and cause hepatitis. Less frequently, they cause myalgia and rhabdomyolysis.

10. Bile Acid-Binding Resins They have excellent safety record and are valuable for patients cannot tolerate other drugs and young patients who may need to take drug long time. The bile acid-binding resins are large polymers containing Cl - that can be exchanged for bile acids in the gut. The bile acid-resin complex is excreted in feces. This action prevents the enterohepatic cycling of bile acids and obligates the liver to synthesize replacement bile acids from cholesterol. To obtain more cholesterol for this purpose, the liver increases the number of LDL receptors. Then the levels of LDL cholesterol in the serum are reduced as more cholesterol is delivered to the liver. They may cause constipation and they can bind, In the gut, to digoxin, thyroxin, warfarin, and other drugs.

11. Fibric Acid Derivatives They activate lipoprotein lipase, promoting the delivery of triglycerides to adipose tissue. They also interfere with the formation of VLDL in the liver. They cause rhabdomyolysis and myopathies. For this reason, the combination of reductase inhibitors and fibrates should be avoided. Niacin (nicotinic acid) Niacin is a vitamin, converted in the body to enzyme cofactors (NAD and NADP) required for oxidative reactions in intermediary metabolism. The quantity of ingested in food does not have effect on serum lipids. The action on lipids requires the administration of several grams of niacin each day. These large doses reduces hepatic VLDL secretion and enhances VLDL clearance by activating lipoprotein lipase. Niacin is probably the most effective single drug for mixed hyperlipidemia. Niacin can elevate serum transaminases and cause hepatitis. It may activate peptic ulcer. Niacin may aggravate diabetes.

12. Estrogens -Estrogens have been demonstrated to protect women against atherosclerosis, largely by increasing HDL cholesterol levels. Vitamin E and Other Antioxidants Vitamin E and other naturally occurring antioxidants may have a protective effect against atherosclerosis by preventing the oxidation of LDL cholesterol.