Statins: Mechanisms & side effects Activation of inducible nitric oxide
synthase, in endothelial cells, systemically
↑ Nitric oxide ↑ Vasodilation
Competitive inhibition of HMG-CoA reductase activity (rate controlling enzyme of cholesterol production)
↓ Mevalonate acid (cholesterol precursor) production in the mevalonate pathway (metabolic processes that produce cholesterol)
↓ Cholesterol ubiquinone (CoQ10) production
↓ Ubiquinone (protective of cellular oxidative effects)
Impaired mitochondrial function
↓ Cyclooxygenase-2 (COX2) expression (enzyme involved in the production of prostaglandins)
↓ Availability of
arachidonic acid (derivative of LDL cholesterol breakdown)
↓ Thromboxane A2 (lipid with prothrombotic properties)
↓ Platelet adhesion
↓ Thrombogenicity (tendency to generate blood clots)
Improved endothelial function
Improved myocardial blood flow
↓ Intrinsic cholesterol biosynthesis in the liver
Compensatory mechanisms
↓ Isoprenoid production (electron & proton carriers)
↓ Isoprenoid intermediates
↓Inflammatory signaling proteins
↓Proliferation of macrophages
↓ Inflammation
Upregulation of hepatic LDL receptors
↑ Hepatic LDL uptake
↓ Serum low-density lipoprotein (LDL)
↑ Apolipoprotein A1 (component of HDL) production
↑ High-density lipoprotein (HDL) Carries serum
cholesterol back to liver
↓ Serum apolipoprotein B levels (acts as a tag for LDL, facilitating uptake by LDL receptors)
↑ Oxidative Stress Hepatocyte damage & inflammation ↑ Serum liver enzymes Hepatotoxicity
↓ ATP
↓ Serum cholesterol
↓ Muscle membrane stability
Rhabdomyolysis (muscle breakdown)
Author: Rupali Manek, Andrew Wu, Rafael Sanguinetti, Luiza Radu Reviewers: Joshua Dian, Laura Byford-Richardson, Alexander Ah-Chi Leung* * MD at time of publication
Stabilization of plaques
↓ Atherosclerosis (plaque build-up in arteries)
↓ Coronary events & mortality
Legend:
Pathophysiology
Mechanism
Sign/Symptom/Lab Finding
Physiological outcome
Published Jan 9, 2017; updated Nov 22, 2024 on www.thecalgaryguide.com