Lipid Lowering Medications Flashcards
Mechanism of Statins
Inhibit HMG-CoA reductase, preventing synthesis of mevalonate in the liver and decreasing LDL-c. Also increases expression of LDLR on liver surface, lowering LDL-c even more
Clinical effects of Statins
Reduce LDL-c by 20-60%, reduce relative risk of CVD by 20%
What are the high potency Statins?
Atorvastatin and rosuvastatin
What are the 3 major side effects of Statins?
Hepatotoxicity (measured using ALT/AST, 3x normal limit is considered acceptable), myopathy (due to CYP3A4 inhibition), diabetes (increased risk for developing it)
Which Statins can you use to avoid potential myopathy and why?
Rosuvastatin, pravastatin, fluvastatin; these statins do not inhibit CYP3A4
Which Statins are metabolized by CYP3A4? CYP2C9? Neither?
CYP3A4: atorvastatin, simvastatin, lovastatin, basically all the other statins
CYP2C9: rosuvastatin, fluvastatin
Neither: pravastatin
Which two compounds increase the toxicity of all statins?
Cyclosporine (immune suppressant) and grapefruit juice (inhibits CYP activity in the intestines)
Mechanism of PCSK9 inhibitors
Inhibit PCSK9, which is normally produced in the liver to inhibit LDLR localization to the surface
Clinical administration and effects of PCSK9 inhibitors
IV administration. Reduces LDL-c by an additional 50% when used in conjunction w/a high potency statin. Commonly used in patients w/Familial Hypercholesterolemia
Side effects of PCSK9 inhibitors
Myalgias, delirium, dementia
Mechanism of Ezetimibe
Blocks NPC1L1 transporter on enterocytes, lowering dietary cholesterol uptake
Clinical effects of Ezetimibe
Lowers LDL-c by 20%
Side effects of Ezetimibe
Digestive issues (diarrhea, bloating, etc.) but NO drug-drug interactions
Mechanism of Bile Acid Sequestrants
Bind bile acids in the gut to prevent reuptake, forcing the liver to synthesize more using cholesterol and resulting in increased LDLR and decreased LDL-c
Clinical effects of Bile Acid Sequestrants
Lowers LDL-c by 20%
Naming of Bile Acid Sequestrants
Cole/chole prefix (cholestyramine, colestipol, etc.)
Side effects of Bile Acid Sequestrants
Digestive issues (hemorrhoids, constipation, bloating, etc.), may interfere w/oral drug uptake
Mechanism of Fibrates
PPARα agonist
Inhibit VLDL secretion (decrease LDL-c)
Inhibit ApoC3, a protein that normally inhibits LPL (decrease TGs)
Promote ApoA1 synthesis (increase HDL-c)
Clinical effects of Fibrates
Used clinically to lower TGs by 20-50% Also: Lowers LDL-c by 5-20% in patients w/normal TGs Raises LDL-c in patients w/high TGs Raises HDL-c by 10-20%
Naming of Fibrates
“fibr” in the name (fenofibrate, clofibrate, gemfibrozil, etc.)
Mechanism of Niacin
Inhibit ApoA1 degradation (increase HDL-c)
Inhibit TG synthesis in liver (decrease TGs, VLDL/LDL-c)
Inhibit TG mobilization in adipose (decrease TGs)
Clinical effects of Niacin
Used clinically to lower TGs by 20-50%
Also:
Lowers LDL-c by 5-25% in patients w/normal TGs
Raises HDL-c by 15-25%
Side effects of Fibrates
Dyspepsia (indigestion), myopathy, gallstones
Contraindications of Fibrates
Severe renal disease or sever hepatic disease
