HMG-CoA reductase inhibitors.pptx

HMG-CoA reductase inhibitors

1. Dr. Kumbhare Manoj R. Professor S.M.B.T . College of Pharmacy Dhamangaon Nashik (M.S .). HMG- CoA reductase inhibitors

2. After successful completion of topic, a learner should be able to- Understand HMG- CoA reductase inhibitors or statins Know examples of statins Explain applications of statins Learning Outcome

3. Introduction Mechanism of statins Examples of statins Applications of statins Content

4. HMG- CoA reductase inhibitors also known as  Statins , are a class of lipid-lowering drugs that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Reduce risk for illnesses related to atherosclerosis, with a varying degree of effect depending on underlying risk factors and history of cardiovascular disease. Clinical practice guidelines generally recommend people start with lifestyle modification through a cholesterol-lowering diet and physical exercise. Introduction

5. Low-density lipoprotein (LDL) carriers of cholesterol play a key role in the development of atherosclerosis and coronary heart disease via the mechanisms described by the lipid hypothesis. Statins are effective in lowering LDL cholesterol and so are widely used for primary prevention in people at high risk of cardiovascular disease, as well as in secondary prevention for those who have developed cardiovascular disease

6. Mechanism The HMG- CoA reductase pathway, which is blocked by statins via inhibiting the rate limiting enzyme   HMG- CoA reductase . Statins act by competitively inhibiting HMG- CoA reductase , the rate-limiting enzyme of the  mevalonate pathway . Because statins are similar in structure to HMG- CoA  on a molecular level, they will fit into the enzyme's active site and compete with the native substrate (HMG- CoA ). This competition reduces the rate by which HMG- CoA reductase  is able to produce  mevalonate , the next molecule in the cascade that eventually produces cholesterol.

7. Inhibiting cholesterol synthesis By inhibiting HMG- CoA reductase , statins block the pathway for synthesizing cholesterol in the liver. This is significant because most circulating cholesterol comes from internal manufacture rather than the diet. When the liver can no longer produce cholesterol, levels of cholesterol in the blood will fall. Cholesterol synthesis appears to occur mostly at night   so statins with short   half-lives   are usually taken at night to maximize their effect. Studies have shown greater LDL and total cholesterol reductions in the short-acting   simvastatin   taken at night rather than the morning,   but have shown difference in the long-acting   atorvastatin .

8. Statin Structre Atorvastatin Cerivastatin

9. Fluvastatin

10. L ovastatin Mevastatin Pitavastatin Pravastatin Rosuvastatin Simvastatin

11. Applications For the primary prevention of cardiovascular disease, the United States Preventive Services Task Force (USPSTF) 2016 guidelines recommend statins for those who have at least one risk factor for coronary heart disease, are between 40 and 75 years old, and have at least a 10% 10-year risk of heart disease. Risk factors for coronary heart disease included abnormal lipid levels in the blood, diabetes mellitus, high blood pressure, and smoking. They recommended selective use of low-to-moderate doses statins in the same adults who have a calculated 10-year cardiovascular disease event risk of 7.5–10% or greater.In people over the age of 70, statins decrease the risk of cardiovascular disease but only in those with a history of heavy cholesterol blockage in their arteries

12. Summary Introduction Mechanism of statins Examples of statins Applications of statins