Antihyperlipidemic Agents: Mechanism of Action

Mechanism of Action of Statins

• Statins inhibit HMG-CoA reductase, a rate-limiting enzyme in the mevalonate pathway, thereby reducing hepatic cholesterol synthesis
• This leads to increased clearance of low-density lipoprotein (LDL) cholesterol from the bloodstream, resulting in decreased serum LDL levels

Inhibiting HMG-CoA Reductase

• Inhibiting HMG-CoA reductase reduces the production of mevalonate, a precursor to cholesterol
• This reduction in mevalonate leads to increased expression of LDL receptors, enhancing LDL uptake in the liver

Administering Statins with Bile Acid Sequestrants

• When used in combination with bile acid sequestrants, statins should be administered at least 2 hours before or 4-6 hours after taking the sequestrant
• This timing helps minimize the potential for reduced statin absorption due to bile acid sequestration

Compensatory Mechanism

• Inhibition of HMG-CoA reductase by statins induces an increase in HMG-CoA reductase expression, a compensatory response to maintain cholesterol synthesis
• This compensatory mechanism can lead to drug resistance and decreased statin efficacy over time

Combination Therapy with Niacin or Ezetimibe

• Statins can be used in combination with niacin to enhance LDL reduction and improve high-density lipoprotein (HDL) levels
• Combination therapy with ezetimibe, an intestinal cholesterol absorption inhibitor, can further reduce LDL levels and improve cardiovascular outcomes