Lipid lowering agents
Lipid lowering agents
| Drug | Mechanism of action | Adverse effect | Indication |
| Hydroxymethyl-glut-aryl coenzyme A (HMG CoA) reductase inhibitors: statins such as atorvastatin, lovastatin, rosuvastatin, simvastatin, etc. | Decrease cholesterol synthesis by inhibiting the rate-limiting enzyme in cholesterol synthesis. This indirectly activates SREBP 2*, which increases LDL receptor expression on the cell surface and increases cellular uptake of LDL. | Myalgia, myopathy, increased creatine kinase, myositis, rhabdomyolysis, hepatotoxicity, elevated liver enzymes; combining a statin with gemfibrozil or niacin increases the risk of severe myopathy. | Lower LDL; lower triglycerides; raise HDL |
| Ezetimibe | Inhibits NPC1L1 (Niemann-Pick C1-like 1), an intestinal protein that promotes cholesterol absorption. | Elevated liver enzymes, diarrhea | Lower LDL |
| Fibrates: gemfibrozil, fenofibrate | Activate PPAR** alpha, which increases oxidation of free fatty acids, decreases hepatic triglyceride synthesis, and increases expression of lipoprotein lipase. | Myopathy, cholesterol gallstones | Lower triglycerides; increase HDL; lower LDL |
| Bile acid sequestrants/resins: cholestyramine, colestipol | Prevent enterohepatic recycling of bile acids. This increases hepatic use of cholesterol to form bile acids, which decreases serum cholesterol levels and increases LDL receptor synthesis. | Nausea, GI upset, decreased absorption of drugs and fat-soluble vitamins | Lower LDL |
| Niacin (vitamin B3) | Inhibits release of fatty acids from adipose tissue, decreases hepatic uptake of fatty acids, and decreases hepatic triglyceride synthesis. | Skin flushing, dizziness, hypotension, tachycardia, itching, gout, diarrhea, hyperglycemia/diabetes, liver damage; flushing occurs due to increased arachidonic acid and prostaglandin D2 and E2 with cutaneous vasodilation. Aspirin taken 30 minutes before niacin prevents flushing. | Lower triglycerides; lower LDL; increase HDL |
| Omega three fatty acids | Decrease hepatic synthesis and secretion of VLDL; increase activity of lipoprotein lipase; decrease lipogenesis; anti-inflammatory. | Headache, nausea, diarrhea, heartburn, bleeding tendency if used with anticoagulants | Lower triglycerides |
| PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors: evolocumab and alirocumab (monoclonal antibodies to PCSK9) | Inhibit PCSK9, an enzyme that degrades LDL receptors. | Myalgia, delirium, dementia | Lower LDL; lower triglycerides; increase HDL |
| Inhibitors of apolipoprotein B synthesis: mipomersen | Inhibits Apo B synthesis in the liver. | Injection site reactions, flu-like syndrome, headache, elevation of liver enzymes | Lower LDL; lower VLDL; lower Lp(a) |
| Inhibitors of microsomal triglyceride transfer protein (MTP): lomitapide | Binds to and inhibits MTP, preventing transfer of triglycerides to Apo B. | Nausea, gastrointestinal upset, elevation of liver enzymes | Lower LDL, especially in patients who lack LDL receptors |
*SREBP 2 is sterol regulatory element binding protein
**PPAR alpha is peroxisome proliferator activated receptor alpha