Statins

Mechanism of Action

1.       Inhibits HMG-CoA reductase, the rate-determining enzyme in endogenous cholesterol synthesis.

2.       Results in:

a.       Increased synthesis of LDL receptors in the liver.

b.       Increased clearing of LDL from the circulation.

c.       Decrease in plasma total cholesterol and LDL cholesterol.

3.    Most effective for reducing LDL (20 – 60%).

4.       Modest effects on increasing HDL (5 – 15%).

Pharmacokinetics

1.       Lovastatin and simvastatin are pro-drugs while pravastatin and fluvastatin are active drugs.

2.    Well absorbed orally.

3.       Lovastatin undergoes extensive metabolization in the liver.

Clinical use

1.       Adjunct to dietary therapy.

2.       Decrease elevated serum total and LDL cholesterol in treatment of primary types IIa and IIb hyperlipidaemias.

3.        Useful when taken alone or with bile acid-binding resins or nicotinic acid to treat elevated levels of LDL.

4.        They should preferably be given in the evening so that their effects coincide with the pattern of cholesterol biosynthesis.

Side effects

1.       CNS: dizziness, insomnia.

2.    GI: constipation, diarrhea, nausea, stomach pain.

3.    GU: impotence.

4.       Musculo-skeletal: myalgia, myositis, rhabdomyolysis.

Drug interactions

1.    The following drugs increase plasma statin levels:

a.       Gemfibrozil.

b.       Macrolides.

c.    Anti-fungal azoles.

d.       Protease inhibitors.

e.       Cyclosporine.

f.       Verapamil.

g.       Diltiazem.

2.       Lovastatin displaces warfarin from protein binding.