AntiHyperlipidaemic Agents 1.pptx

AntiHyperlipidaemic Agents 1.pptx

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  ANTIHYPERLIPIDAEMIC AGENTS PRESENTED BY: SAMEENA RAMZAN M.PHARMA1st Year BRANCH: Pharmaceutical chemistry • Department of pharmaceutical sciences university of Kashmir Hazratbal Srinagar
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  Outline of thepresentation: Introduction Classification Synthesis Mechanism of Action
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  Hyperlipidaemia
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  • There are4 main classes of lipoprotein, differing in the relative proportion of the core lipids and in the type of apoprotein. • They also differ in size and density on which basis they are classified as; 1. High density lipoproteins (HDL) 2. Low density lipoproteins (LDL) 3. Very low-density lipoproteins (VLDL) 4. Chylomicrons Various types of hyperlipidemia are found. a. Primary: the plasma triglycerides and cholesterol concentration are raised, and particular-lipoprotein classes are increased. b. Secondary: they occur because of diabetes, alcoholism, liver disease and by some drugs like chlorthalidone, corticosteroids.
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  Anti Hyperlipidaemic Agents Hypolipidaemicdrugs are those which lower the levels of lipids and lipoproteins in blood. The hypolipidemic drugs have attracted considerable attention because of their potential to prevent cardiovascular disease by retarding the accelerated atherosclerosis in hyperlipidemic individuals. The high risk of atherosclerosis is associated with an increased plasma cholesterol and a high LDL:HDL ratio.
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  • The current pharmacotherapy includesthe following: 1. HMG CoA reductase (or 3-hydroxy-3- methyl-glutaryl-CoA reductase or HMGR) inhibitors (statins). 2. Bile acid sequestrants (resins). 3. Drugs that activates lipoprotein lipase (fibric acid derivatives). 4. Drugs that inhibit lipolysis and triglyceride synthesis (nicotinic acid). Combined therapeutic regimen is useful in the following cases: • When LDL levels are insignificantly increased during treatment of hypercholesterolemia with a resin. • When LDL and VLDL levels are both elevated initially. • When LDL and VLDL levels are normalized with a single agent. • When elevated level of lipoprotein or HDL deficiency coexist with other hyperlipidaemias.
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  Classification • Antihypercholestaerolemic agentsact either by reducing the production of lipoproteins or by their removal • from blood. • I. HMG CoA—Reductase Inhibitors
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  Synthesis and drugprofile • I. HMG CoA-Reductase Inhibitors • Mode of action: These kinds of drugs competitively inhibit the conversion of 3-hyroxy-3-methyl glutaryl coenzyme (HMG CoA) to mevalonate, which is the rate-limiting step in cholesterol synthesis and results in receptor mediated uptake and catabolism of intermediate density lipoprotein and very low-density lipoprotein
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  Lovastatin: Lovastatin is produced commerciallyvia a multi-stage fermentation process which originates from cultures of a strain of Aspergillus terreus. This is the first clinically used statin, which is lipophilic and given orally in the precursor lactone form.
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  7-[3-(4-Fluorophenyl)-1-(1-methylethyl)-1H-indol-2-yl]-3,5- dihydroxy-hept-6-enoic acid
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  synthesis
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  Mechanism of action:(statins) • Statins competitively inhibit conversion of 3-Hydroxy-3- methyl glutaryl coenzyme A to mevalonate which is the rate limiting step in the synthesis of cholesterol by the enzyme HMG-COA reductase Effect on plasma lipids (%): 1. LDL: ↓ 20-55 2. HDL: ↑ 5-15 3. TG: ↓ 10-35
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  Drug Profile ofFibric acid derivatives CLOFIBRATE uses: • It is a drug of choice in the treatment of type III, IV, and V hyperlipoproteinaemias.
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  Synthesis
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  Gemfibrozil: • USES: • Gemfibrozilis the first line drug for patients with markedly increased TG levels irrespective of CH levels. • It is most effective in type III hyperproteinaemia also beneficial for type IV and V.
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  Synthesis
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  Mechanism of action(fibrates) These drugs activate receptors called α-peroxisome proliferator- activated receptors, which enhance the synthesis of lipoprotein lipase and increase the degradation of very low-density lipoprotein. This also enhances the fatty acid oxidation. Effect on plasma lipids (%): LDL : ↓ 5-15 HDL : ↑ 10-20 TG : ↓ 20-50
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  Bile Acid Sequestrants 1.Cholestyramine resin: Effect on lipid profile (%) LDL: ↓ 15-25 HDL: ↑ 3-5 TG: not affected, may increase in some It is a styrene copolymer with divinyl benzene and quaternary ammonium functional group. The resin is insoluble in water, remains unchanged in the intestinal tract, unaffected by digestive enzymes, and is not absorbed. These are basic ion exchange resins, which binds with bile acids, interferes in the enterohepatic circulation and leads to the excretion of cholesterol in faeces. This also indirectly leads to the enhanced hepatic metabolism of cholesterol to bile acids, so more LDL receptors are exposed on liver cells and the plasma intermediate density and very low-density lipoprotein clearance is more.
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  Pyridine derivative Nicotinic acid: Synthesis:
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  Mechanism of Action: Nicotinic acidinhibits the lipolysis of triglycerides by hormone sensitive lipase, which reduces transport of the free fatty acids to liver and decreases hepatic triglycerides synthesis. Reduction of triglycerides synthesis decreases the production of hepatic VLDL. Effect on plasma lipids (%): 1.LDL : ↓ 15-25 2.HDL : ↑ 20-35 3.TG : ↓ 20-50
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  References: Textbook of MedicinalChemistry Vol-I by V. Alagarsamy Medicinal Chemistry by D. Sriram. P. Yogeeswari Essentials of Medical Pharmacology by K.D. Tripathi 8th Edition Foye’s principle of Medicinal Chemistry
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  THANK YOU