Bile acid sequestrans (cholestyramine and colestipol)
- MOA: positively charged large molecules that bind negatively charged bile acids.
- Effects on lipids: LDL reduction is dose dependent, triglycerides may increase transiently, HDL increase (4-5%)
-S/E: GI intolerance
- MOA: inhibits lipolysis of triglycerides by hormone-sensitive lipase. In the liver reduces triglyceride synthesis by inhibiting synthesis and esterification of fatty acids (increase ApoB degradation)
- Effect on lipids: reduces triglycerides (35-50%), reduces LDL (25%), HDL increases (more in pts with low HDL levels to begin with)
-S/E: flushing, dyspepsia, can reactivite PUD, hepatotoxicity
Fibric acid derivatives (fenofibrate, gemfibrozil)
- MOA: remains unclear, ?PPAR isotype
- Effects on lipids: depends on starting lipid levels, genetic hyperliproteinemia. Type III hyperliproteinemia are among most sentivite (triglyceride and cholesterol levels are lowered, xanthomas regress, angina/claudication improve). Mild hypertriglyceridemia can decrease triglycerides by 50% increase HDL 15%, LDL is unchanged. Higher triglycerides (400-1000 mg/dl), triglycerides fall but LDL increases
- S/E: GI intolerance, rash, hairloss, myalgias, fatigue, headache, impotence, anemia. Potentiate effects of anticoagulants
- MOA: inhibits luminal cholesterol uptake by jejunal enterocytes by inhibiting NPC1L1
- Effect on lipids: decrease LDL by 15-20%. Combination with statin leads to greater decrease in LDL than by either product alone.
-S/E: no specific adverse effects.
- MOA: competitively inhibits HMG-CoA reductase (inhibits rate limiting step of cholesterol biosynthesis)
- Effect on lipids: decreases LDL, triglycerides >250 are decreased, small increase in HDL
-S/E: hepatotoxicity, myopathy