STEPTRACKERPHARMACOLOGY + BIOCHEMISTRY | CARDIOVASCULAR | HIGH-YIELD REVIEW
Lipid-Lowering Drugs
Statins dominate because they lower LDL and cardiovascular events; the other classes add LDL lowering or target triglycerides, each with a signature adverse effect.
FOCUS ON
Statins inhibit
HMG-CoA reductase → ↓ hepatic cholesterol → ↑
LDL receptors → ↓↓ LDL; ↓ CV events and mortality. Adverse:
myopathy/rhabdomyolysis (↑ with fibrates, niacin, CYP3A4 inhibitors), ↑ LFTs, new diabetes; teratogenic.
Ezetimibe: blocks
NPC1L1 in intestine → ↓ cholesterol absorption.
PCSK9 inhibitors (alirocumab, evolocumab; inclisiran siRNA): ↑ LDL-receptor recycling → ↓↓ LDL.
Bempedoic acid: ACL inhibitor (upstream of HMG-CoA reductase), not active in muscle.
Bile acid sequestrants (cholestyramine, colesevelam): ↓ LDL, ↑ TG, GI upset, bind other drugs and fat-soluble vitamins.
Fibrates (gemfibrozil, fenofibrate): PPAR-α → ↑ LPL → ↓↓
TG; myopathy with statins (gemfibrozil),
cholesterol gallstones.
Niacin: ↓ VLDL, ↑ HDL;
flushing (prostaglandin — aspirin prevents), hyperglycemia, hyperuricemia.
Omega-3 (icosapent ethyl): ↓ TG.