Hyperlipidemia
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This document discusses lipids and hyperlipidemia. It begins by explaining how chylomicrons, LDL, and HDL transport lipids between the intestines and cells. High levels of oxidized LDL can lead to atherosclerosis. Hyperlipidemia is characterized by abnormally high levels of fats and lipids in the blood. It causes atherosclerosis and conditions like heart disease. Various drugs are used to treat hyperlipidemia including statins, fibrates, niacin, bile acid sequestrants, and omega-3 fatty acids. The document explains the mechanisms of these drug classes.
![CLASSIFICATION OF HYPERLIPIDEMIA
TYPES CLASSIFICATION LIPOPROTEIN
INCREASE
PLASMA
LIPOPROTEIN
INCREASE
1 Hypertriglyceridaemia
(Exogenous)
[lipoprotein lipase deficiency]
Increase chylomicrons Triglyceride
2(a) Hypercholesterolemia
(LDL Receptor deficiency)
LDL Cholesterol
2(b) Familial combined
hyperlipoproteinaemia
LDL+VLDL Cholesterol and
Triglyceride
3 Dysbetalipoproteinaemia β(VLDL) Cholesterol and
Triglyceride
4 Hypertriglyceridaemia
(Endogenous)
VLDL Triglyceride
5 Mixed Hypertriglyceridaemia VLDL and
chylomicrons
Triglyceride
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Hyperlipidemia
- 1. MGV'S COLLEGE OF PHARMACY SAGAR BAGUL DEPARTMENT OF PHARMACOLOGY 1SAGAR BAGUL
- 3. LIPID Chylomicrons transport fats from the intestinal mucosa to the liver In the liver, the chylomicrons release triglycerides and some cholesterol and become low-density lipoproteins (LDL). LDL then carries fat and cholesterol to the body’s cells. High-density lipoproteins (HDL) carry fat and cholesterol back to the liver for excretion. When oxidized LDL cholesterol gets high, atheroma formation in the walls of arteries occurs, which causes atherosclerosis. HDL cholesterol is able to go and remove cholesterol from the atheroma. Atherogenic cholesterol → LDL, VLDL, IDL 3SAGAR BAGUL
- 4. HYPERLIPIDEMIA Hyperlipidemia means there is too much cholesterol in the blood Cholesterol is synthesize from acetate in many tissues of the body Maintain the structural integrity of plasma membrane of cells Acetoacetyl –CoA +Acetyl-CoA HMG-CoA HMG-CoA reductase Mevalonate Mavalonate kinase Cholesterol Dig: Biosynthesis of cholesterol 4SAGAR BAGUL
- 5. HYPERLIPIDEMIA Characterized by abnormally high concentration of fats and lipids in the blood. Increase level of low density lipoprotein (LDL) as well as triaglyceride and decrease level of high density lipoprotein. It is a major cause of atherosclerosis and atherosclerosis induced conditions such as coronary heart disease(CHD), unstable angina myocardial infarction (Heart attack). 5SAGAR BAGUL
- 6. Causes Of Hyperlipidemia Acute heaptitis AIDS (protease inhibitors) Diabetes mellitus 6 Diet Hypothyroidism Nephrotic syndrome Obstructive liver disease Obesity Pregnancy SAGAR BAGUL
- 7. CLASSIFICATION OF HYPERLIPIDEMIA TYPES CLASSIFICATION LIPOPROTEIN INCREASE PLASMA LIPOPROTEIN INCREASE 1 Hypertriglyceridaemia (Exogenous) [lipoprotein lipase deficiency] Increase chylomicrons Triglyceride 2(a) Hypercholesterolemia (LDL Receptor deficiency) LDL Cholesterol 2(b) Familial combined hyperlipoproteinaemia LDL+VLDL Cholesterol and Triglyceride 3 Dysbetalipoproteinaemia β(VLDL) Cholesterol and Triglyceride 4 Hypertriglyceridaemia (Endogenous) VLDL Triglyceride 5 Mixed Hypertriglyceridaemia VLDL and chylomicrons Triglyceride 7SAGAR BAGUL
- 8. Medications For Hyperlipidemia Drug Class Agents Effects (% change) Side Effects HMG CoA reductase inhibitors Lovastatin Pravastatin LDL (18-55), HDL (5-15) Triglycerides (7-30) Myopathy, increased liver enzymes Cholesterol absorption inhibitor Ezetimibe LDL( 14-18), HDL (1-3) Triglyceride (2) Headache, GI distress Niacin Nicotinic Acid LDL (15-30), HDL (15-35) Triglyceride (20-50) Flushing, Hyperglycemia, Hyperuricemia, GI distress, hepatotoxicity Fibric Acids Gemfibrozil Fenofibrate LDL (5-20), HDL (10-20) Triglyceride (20-50) Dyspepsia, gallstones, myopathy Bile Acid sequestrants Cholestyramine Colestipol LDL HDL No change in triglycerides GI distress, constipation, decreased absorption of other drugs Omega-3 Fatty acids Eicosapentanoic acid. Fatty acid in liver GI discomfort SAGAR BAGUL 8
- 9. MOA OF HMG-CoA reductase INHIBITOR Lovastatin, Pravastatin Statin competitively inhibit HMG-CoA reductase , the enzymes that catalyzes rate limiting step in choleserol biosynhesis . THERAPEUTIC USES: Hypercholesterolemia Coronary atherosclerosis Familial hypercholesterolemia SERIOUS ADVERSE EFFECTS: Myopathy Hepatotoxicity Abdomonal pain Constipation Diarrhea Nausea 9SAGAR BAGUL
- 10. MOA OF BILE ACID SEQUESTRANTS Colestipol, Cholestvramine Anion exchange resin that lower bile acid concentration Colesevelam newer bile acid sequestrants (oral suspension) Lowers LDL 18 % at it’s maximum dose Fig:MOA OF BILE ACID SEQUESTRANTS 10SAGAR BAGUL
- 11. MECHANISM OF ACTION OF NIACIN Nicotinic acid In adipose tissue niacin inhibit the lipolysis of triglyceride by hormone sensitive lipase Reduces transport of free fatty acids to the liver and decreases hepatic triglyceride synthesis THERAPEUTIC USES: Low HDL with mildly elevated LDL or triglyceride Familial combined hyperlipidemia SERIOUS ADVESE EFFECTS: Hepatotoxicity Flushing Hyperuricemia and gout 11SAGAR BAGUL
- 12. MOA OF CHOLESTEROL ABSORPTION INHIBITORS Ezetimibe • Selectively inhibits absorption of dietary and biliary cholesterol in the small intestine • Reduces delivery of cholesterol to the liver and increases hepatic LDL receptor activity • Thereby increases clearance of circulating LDL particle THERAPEUTIC USES: Familial hypercholesterolemia SERIOUS ADVERSE EFFECTS: Myopathy , Elevated liver function test, Arthralgia, Myalgia, Headache 12SAGAR BAGUL
- 13. MECHANISM OF ACTION OF FIBRATE Gemfibrozil, Finofibrate Inhibit triglyceride synthesis reduces VLDL release into circulation Increase lipoprotein lipase activity, which catabolizes chylomicrons and VLDL Increase catabolism of triglyceride-rich VLDL thereby lowering serum VLDL levels Incease HDL through improve Apo-1 and Apo-2 synthesis 13SAGAR BAGUL
- 14. THERAPEUTIC USES: Hypertriglyceridemia • SERIOUS ADVERSE EFFECTS Myopathy Elevated liver function test Arthralgia Myalgia Headache 14SAGAR BAGUL
- 15. OMEGA -3 FATTY ACIDS Ecosapentanoic acid Regulate nuclear transcription factors that is Sterol Regulating Element Binding Protein (SREBP) and PPARα, to reduce triglyceride biosynthesis Increase fatty acid oxidation in the liver THERAPEUTIC USES: Hypertriglyceridemia ADVERSE EFFECTS: Anaphylaxis GI discomfort 15SAGAR BAGUL
- 16. 16 Fig:-Mechanism for the Decrease in LDL Levels SAGAR BAGUL
- 17. REFERENCES David E. Golan,Armen H.Tashjian,Jr.” Principles Of Pharmacology” The Pathphysiologic Basis Of Drug Therapy , Published by wolters kluwer (India) pvt Ltd ,3rd Edition ,Page no:310 H.L Sharma and K.K Sharma,”Principles of Pharmacology,”Paras Medical Publisher,3rd edition.page no:382 Goodman & Gilman’s, The Pharmacological Basis of Therapeutics,12th edition,page no :311 F.S.K.Barar, “Essentials Of Pharmacotherapeutics” S.Chand & Company Ltd. 1st Ed. 1985, page no:298 17SAGAR BAGUL
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