Ch 20: Inhibitors of Cholesterol Synthesis

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What is the role of statins in cholesterol synthesis?

Competitively inhibit HMG-CoA reductase

What is the consequence of decreased cellular cholesterol concentration?

Activation of SREBP2

What is the function of SREBP2 in the context of cholesterol regulation?

Up-regulates expression of the gene encoding the LDL receptor

What is the consequence of increased LDL receptor expression?

Increased uptake of plasma LDL

What indicates true hepatotoxicity?

Elevations in ALT and AST accompanied by elevations in serum bilirubin concentrations

Which combination results in additive LDL decreases without significant drug interactions?

Statin with a bile acid sequestrant or cholesterol absorption inhibitor

What should be closely monitored when co-administering niacin and a statin?

Development of adverse effects

Which fibrate inhibits both the transport and glucuronidation of statins in the liver?

Gemfibrozil

Which type of statin is preferable in patients taking drugs metabolized by cytochrome P450?

Statin that is not metabolized by P450 enzymes

What may increase the risk of rhabdomyolysis when combined with certain fibrates?

Gemfibrozil

In what type of patients may the combination of niacin and a statin be most useful?

Patients with high levels of LDL cholesterol and low levels of HDL cholesterol

What combination has been reported to be efficacious but may decrease statin clearance?

Fibrates and statins

What is the effect of statins on LDL-cholesterol concentrations?

Reduce by up to about 60%

What is a potential adverse effect of high-potency statins?

Myopathy and/or myositis with rhabdomyolysis

What is the effect of statins on triglyceride concentrations?

Reduce by up to about 40%

What is the mechanism of action of statins?

Reduction of cholesterol synthesis

What is the effect of statins on mortality after a myocardial infarction in primary prevention?

Reduced

What is the primary adverse effect of statins?

Myopathy and/or myositis with rhabdomyolysis

What is the relationship between statin dose and LDL reduction?

Each subsequent doubling of the dose produces an additional 6% LDL reduction

What is the effect of statins on high-risk patients with average or below average LDL-cholesterol levels?

Effective in reducing cardiovascular disease risk

What is the effect of statins on HDL-cholesterol concentrations?

Increase by 10%

What is the evidence for diminished inflammation with statin therapy?

Decreases in acute-phase reactants such as C-reactive protein

What may certain patients with a molecular variant of an organic anion transporter be at higher risk of developing?

Statin-induced myopathy

What is the effect of statins on serum transaminase levels?

High-potency statins can cause increases in serum transaminase levels

Study Notes

Statins and Their Effects

  • Statins have been shown to significantly reduce mortality after a myocardial infarction in both secondary and primary prevention.
  • Statin use is associated with a greater absolute risk reduction in secondary prevention due to higher absolute risk of death in this group.
  • Statins are effective in reducing cardiovascular disease risk for high-risk patients, even with average or below average LDL-cholesterol levels.
  • Statins reduce LDL-cholesterol concentrations by up to about 60%, increase HDL-cholesterol concentrations by 10%, and reduce triglyceride concentrations by up to about 40%.
  • The dose–response relationship of statins is nonlinear, with each subsequent doubling of the dose producing an additional 6% LDL reduction.
  • Statins have pleiotropic effects, including decreased inflammation, reversal of endothelial dysfunction, decreased thrombosis, and improved stability of atherosclerotic plaques.
  • Evidence for diminished inflammation with statin therapy includes decreases in acute-phase reactants such as C-reactive protein.
  • Statins are believed to act by the same mechanism, but differences in potency and pharmacokinetic parameters exist among the seven approved statins.
  • Statins are generally well tolerated, with the main adverse effect being myopathy and/or myositis with rhabdomyolysis, primarily at high doses of the most potent statins.
  • High-potency statins can also cause increases in serum transaminase levels.
  • Plasma creatine kinase levels are not useful for routine monitoring of statin-treated patients.
  • Certain patients with a molecular variant of an organic anion transporter may be at higher risk of developing statin-induced myopathy.

Test your knowledge of statins and their effects with this quiz. Explore the benefits, dosage relationships, pleiotropic effects, adverse effects, and monitoring considerations of statin therapy.

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