1. Anti hyperlipidemic drugs (lipid lowering drugs) Department of Pharmacology Faculty of Medicine AIMST UNIVERSITY 5 September 2012

2.  Lipid Metabolism  Function of Cholestrol  Good Cholestrol – High Density Lipoprotein (HDL)  Bad Cholestrol – Low Density Lipoprotein (LDL)  LDL has strongest link to vascular disease  Cardiovascular risk of high bad cholestrol – mortality and Morbidity : stroke angina myocardial infarct chronic renal insufficiency  renal failure  renal transplant colorectal cancer  Obesity and hypercholestrolemia come hand in hand

3. Class of drugs used to reduce plasma lipid: 1.Statins 2.Fibrate 3.Bile acid-binding resins 4.Niacin– lower LDL and increase HDL, also causes hyperglycemia 5. Ezetimibe– selective inhibitor of dietary cholestrol in the gut 6. Phytosterol – reduce absorption of cholestrol in the gut. 7. Olistat – inhibit pancreatic lipase the enzyme which breakdowns cholestrol in the intestine. ( used to treat obesity)

4. Statins Have similar to HMG-CoA at molecular level Mechanism of action – blocks the pathway for cholestrol synthesis in the liver ; inhibit HMG CoA reductase enzyme in cholestrol synthesis ( rate limiting enzyme) Most of the circulating cholestrol comes from synthesis in the liver other than intestinal absorption. End result  lower the LDL and prevent athersclerotic disease. Shorter acting statins  better to take at bed time because Cholestrol synthesis is highest at night

5. Statins available in the market; 1.Atorvastatin 2.Cerivastatin 3.Fluvastatin 4.Lovastatin 5.Mevastatin 6.Pitavastatin 7.Pravastatin 8.Rosuvastatin 9.Simvastatin

6. Adverse effects  Myalgia  Myositis  Rhabdomyolysis ( pathological break down of skeletal muscle)  GI symptoms – nausea and vomitting Drug interactions  with those drugs metabolized by cytochrome P450 enzyme ( CYP 34A )  Grape fruit or grape fruit juice Naturally occuring statin  oyster mushroom

7. Fibric acid derivatives ( Fibrates ) 1.Gemfibrozil 2.Fenofibrate 3.Bezafibrate Mechanism of action – primarily function as ligands for nuclear transcription receptors thereby decrease triglycerides and cholestrol by stimulating peroxysomal β oxidation pathway Adverse effects – rashes, GI symptoms, myopathy, arrythmias -- increased aminotransferase and alkaline phosphatase

8. Niacin ( vitamin B3) MOA – inhibits VLDL secretion inhibits intracellular lipase of adipose tissue Adverse effects– cutaneous vasodilation pruritus, rashes, dry skin nausea and abdominal discomfort reversable elevation of aminotransferase enzyme

9. Bile acid-binding resins 1.Colestipol 2.Cholestyramine 3.Colesevelam Mechanism of action – the bile acids, metabolites of Cholestrol are normally reabsorbed in the jejunum and ileum. These resins bind bile acids so that they can prevent reabsorption of them. Adverse effects– constipation and bloating malabsorption of vit K should avoid in diverticulitis

10. Inhibitors of intestinal sterol absorption Ezetimebe Mechanism of action – selectively inhibits intestinal absorption of phytosterols and cholestrols.

11. Management of hyperlipidemia Diet  Cholestrol,saturated and trans fats  increase LDL  Total fat,alcohol and excess calorie  increase triglycerides Life style  sedentry life style Drugs  lipid lowering agents