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Uploaded byJasmine Chaudhary
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Antihyperlipidemic.pdf

This document discusses antihyperlipidemic drugs, which are used to treat high lipid levels in the blood. It defines hyperlipidemia and describes the different types of lipoproteins and their roles in transporting fats. The main classes of antihyperlipidemic drugs discussed are HMG-CoA reductase inhibitors (statins), fibric acid derivatives, bile acid sequestrants, LDL oxidation inhibitors, and ezetimibe. The document provides examples of drugs in each class and describes their mechanisms of action and common side effects.

Education◦
Antihyperlipidemic drugs Dr. Jasmine Chaudhary Associate Professor MMCP
Introduction Drugs used to treat hyperlipidemia. Also known as lipid lowering drugs or hypolipidemic. Hyperlipidemia is an increase in lipids which are a group of fats or fat like substances in the blood (due to abnormality in lipid metabolism. Cholesterol and the triglycerides are two lipids in the blood. Elevation of one or both of these lipids is seen in hyperlipidemia. So accordingly classified as • Hyperlipoproteinemia(Increased concentrations of lipoproteins)/ • Hypercholesterolemic (high concentration of cholesterol)/ • Hypertriglyceridemia (high concentration of triglyceride)
 Serum cholesterol levels above 240 mg/dL and triglyceride levels above 150 mg/dL are associated with atherosclerosis.  Atherosclerosis is a disorder in which lipid deposits accumulate on the lining of blood vessels, eventually producing degenerative changes and obstruction of blood flow. Atherosclerosis is considered to be a major contributor in the development of heart disease.
Lipids are water insoluble whereas blood and other body fluids are watery so they need a special transport which is carried through protein and this complex is called lipoprotein and the protein moiety of a lipoprotein is called apolipoprotein which allow fats to move through the water inside and outside cells.
There are different types of lipoproteins which differ from each other w.r. t to size, density and relative proportion of triglycerides and cholesterol  Chylomicrons (CM). •Very Low Density Lipoprotein (VLDL). •Low Density Lipoprotein (LDL). •Intermediate Density Lipoprotein (IDL). •High Density Lipoprotein (HDL)
 HDL stands for high-density lipoproteins. It is called the "good" cholesterol because it carries cholesterol from other parts of your body back to liver. Liver then removes the cholesterol from body.  LDL stands for low-density lipoproteins. It is called the "bad" cholesterol because a high LDL level leads to a buildup of cholesterol in arteries.
Causes • Lifestyle habits (not exercising, and smoking) • Obesity, diabetes, kidney disease, pregnancy, and an under active thyroid gland. • Inherit hyperlipidemia
Classification of Antihyperlipidemic Drugs • HMG-CoA-reductase Inhibitor: e.g. Lovastatin, Simvastatin, Pravastatin • Fibric acid derivatives: e.g. Clofibrate, Fenofibrate, Ciprofibrate, Benzafibrate, Gemfibrozil • Bile-acid sequestrants: e.g. Cholestyramine, Colestipol • Inhibition of LDL oxidation: e.g. Probucol • Cholestrol absorption inhibitor: Ezetimibe • Miscellaneous Agents: e.g. Nicotinic acid, Neomycin, β-Sitosterol, Acipimox, Metformin, Dextrothyroxine.
HMG CoA-reductase Inhibitors: Most effective and best tolerated drugs These drugs bring about specific, reversible and competitive blockage of HMG-CoA reductase (3-Hydroxy-3-methyl-glutaryl- CoA reductase), the enzyme that catalyzes the conversion of HMG- CoA to mevanolate. This reaction is the rate-determining step in the synthetic pathway of cholesterol leading to decreased hepatic cholesterol synthesis. HMG-CoA reductase HMG-CoA Mevalonic acid Cholesterol There are two classes of statins: • Natural Statins:Lovastatin, Compactin, Pravastatin, Simvastatin • Synthetic Statins: Atorvastatin, Fluvastatin
Lovastatin 8-{2-[4-Hydroxy-6-oxo-oxan-2-yl]ethyl}-3,7-dimethyl- hexahydronaphthalenyl-2-methylbutanoate
Lovastatin is a prodrug, an inactive lactone in its native form. It is hydrolysed in vivo to the β-hydroxy acid open ring form; which is the active form. Adverse effects  Mild, transient GI disturbances  Rash  Headache  Myopathy (muscle pain)  Elevations in liver enzymes or liver disease
Fibric acid derivatives • Fibrates are 2-phenoxy-2-methyl propanoic acid derivatives. These drugs stimulate β-oxidation of fatty acids in mitochondria. Mode of Action • Decrease plasma TGs levels more than cholesterol levels • Fibrates lower blood triglyceride levels by reducing the liver's production of VLDL (the triglyceride-carrying particle that circulates in the blood) by stimulating enzyme lipase and by speeding up the removal of TGs from the blood. • Fibrates also are modestly effective in increasing blood HDL cholesterol; however, fibrates are not effective in lowering LDL cholesterol. e.g: Clofibrate, Fenofibrate, Gemfibrozil
Adverse effects • Abdominal discomfort, diarrhea, nausea • Blurred vision, headache • Increased risk of gallstones • Malignancy Ethyl-2-(4-chlorophenoxy)-2-methyl propanoate
Bile acid Sequesterents  Also called Bile acid–binding resins and ion-exchange resins. E.g. cholestyramine and colestipol.  Bile acids are the metabolic end-products of cholesterol which are released into the intestine and aid in dissolution and absorption of lipids. Major fraction (about 98%) of bile acids released into the gut is reabsorbed through enterohepatic circulation and suppresses the microsomal hydroxylase enzyme involved in the conversion of cholesterol to the bile acids. Thus due to enterohepatic reabsorption of the bile acids further cholesterol metabolism is suppressed.
Cholestyramine and colestipol are the examples of bile acid-binding resins which form a sort of non-absorbable complex with bile acids due to the presence of quaternary nitrogen. Thus these drugs promote their elimination from the gut and inhibit their reabsorption into the circulation. ADR: •Constipation • Heartburn, nausea, bloating [4-[3-(4-ethylphenyl)butyl]phenyl]-trimethylazanium
Cholestipol Side effects include: Gastrointestinal tract disturbances
Inhibition of LDL oxidation: The antioxidant effects of agents of this group inhibit the oxidation of LDL, thereby, preventing its uptake by macrophages. This may help prevent development of atherosclerosis. E.g Probucol Cholestrol absorption inhibitor: Ezetimibe It is a drug that lowers plasma cholesterol levels by decreasing cholesterol absorption in the intestine.
Miscellaneous Niacin (A water soluble vitamin of the B family) • Increases activity of lipase, which breaks down lipids • Reduces the metabolism of cholesterol and triglycerides Adverse effects • Flushing (due to histamine release) • Pruritus • GI distress
 β – Sitotsterol: It is a plant sterol. Due to the structural similarity with cholesterol, this agent impedes the absorption of dietary cholesterol and produces a moderate reduction in cholesterol level. Its low efficacy and high cost decrease its popularity as lipid lowering agent.