Wider use of statins may help preventing heart attacks

Statins are drugs which help in reducing the cholesterol level by blocking the enzyme, HMG CoA Reductace, which is an important component in lipid metabolism.Statins are prescribed in all patients attending hospital with acute coronary syndromes and are given to people who are at high risk for coronary events.

Statins reduce significantly the incidence of coronary events,  being the most efficient hypolipidemic compounds that have

reduced the rate of mortality in coronary patients.

Decrease in LDL cholesterol>>>>antiatherosclerotic effects>>>>Prevent acute coronary syndromes.

Statins act by inhibiting HMG-CoA reductase, which is vital in Cholesterol synthesis. They can exert antiatherosclerotic effects independently of their hypolipidemic action.

Other Advantages

Mevalonate, the product of HMG CoA reductase reaction, is the precursor not

only for cholesterol, but also for many other nonsteroidal

isoprenoidic compounds, inhibition of this

key enzyme may result in pleiotropic effects.

Actions of Statins

Cholesterol Biosynthesis

• Inhibition of cholesterol biosynthesis,
• increased uptake and degradation of low density lipoproteins (LDL),
• inhibition of the secretion of lipoproteins,
• inhibition of LDL oxidation,
• inhibition of the scavenger receptorsexpression

In preventing acute coronary syndromes

• The plaque instability, manifestedas an ulceration of the fibrous cap, the rupture of the

  plaque and internal hemorrhage, are characteristics

  of the plaques with numerous lipid deposits and

  macrophages in the cap

• Statins promoste plaque stability
• statins (fluvastatin, simvastatin) can inhibit t he gelatinolytic activity ofmetalloproteases, as well as their secretion by

  human macrophages in culture.

Others

• statins interfere with events involved in bone formation and impede tumor cell growth.
• Reduction of the accumulation of esterifiedcholesterol into macrophages
• Increase of endothelialNO synthetase,
• reduction of the inflammatoryprocess,
• Increased stability of the atherosclerotic plaques,
• Restoration of platelets activity and of the coagulation process
• Human subjects treated with statins have shown a reduction in the number of bone fractures

How statins are Obtained

Some of the statins are obtained after fungal

fermentation: lovastatin , pravastatin

and simvastatin others

by synthesis: fluvastatin , atorvastatin

, and cerivastatin.

Five statins are, at this moment, in

clinical use: lovastatin, simvastatin, pravastatin,

atorvastatin and fluvastatin.

Adverse effects of statin therapy

The most important adverse effects are liver and muscle

involvement. Myopathy can occur if

cytochrom P450 or other inhibitors of statins

metabolism are co-administered with statins,

Azole antifungals

Fibrates and niacin enhance myopathy risk

Other risk factors are: liver

damage, renal insufficiency, hypothyroidism.