Antihyperlipidemic Agents

Question 1

Gemfibrozil

Fenofibrate

Answer 1

Fibrates
Mechanism: bind and activate peroxisome-proliferator-activated receptor alpha (PPAR-alpha)–>increases HDL, decreases triglycerides
Use: reduce VLDL (triglycerides), LDL, increase HDL; primary chylomicronemia, familial hypertriglyceridemia, familial combined hyperlipoproteinemia, familial dysbetalipoproteinemia, secondary hypertriglyceridemia
Adverse effects: rashes, GI symptoms, myopathy (increases with use of statins)

Question 2

Cholestyramine
Colesevelam
Colestipol

Answer 2

Bile acid-binding resins
Mechanism: bind bile acids and salts–>can’t be reabsorbed so excreted in feces–>liver must synthesize bile acids to replace–>decrease cholesterol–>increase hepatocyte expression of LDL receptors–>LDL plasma decreases
Use: combo with statins for hypercholesterolemia (familial hypercholesterolemia), used in children and pregnant women
Adverse effects: increase plasma triglycerides, bloating, constipation

Question 3

Niacin

Answer 3

Mechanism: bind G protein-coupled receptor on adipocytes–>decrease adipocyte hormone sensitive lipase activity–>decrease VLDL and LDL; increases apo A-I–>increase HDL
Use: hypertriglyceridemia and hypercholesterolemia
Adverse effects: cutaneous flushing and itching (reduce with NSAID), hyperuricemia (gout), hepatotoxicity, statin-induced myopathy, risky in combo with lovastatin (best with fluvastatin)

Question 4

Ezetimibe (Zetia)

Answer 4

Inhibitors of cholesterol absorption
Mechanism: inhibits Niemann-Pick C1-like proteins–>blocks intestinal absorption of cholesterol–>reduced chylomicron remnants delivered to liver–>increased expression of hepatic LDL receptors–>decrease LDL
Use: familial combined hyperlipoproteinemia, familial hypercholesterolemia, familial ligand-defective apoB
Adverse effects: great safety profile

Question 5

Atorvastain
Fluvastatin
Lovasatin
Pitavastatin
Rosuvastatin
Simvastatin

Answer 5

Inhibitors of HMG-CoA reductase (Statins)
Mechanism: competitively inhibit HMG-CoA reductase (rate limiting enzyme–>reduce cholesterol synthesis–>up-regulate LDL receptors; pleiotropic effect=protective cardiovascular effects
Adverse effects: myopathy, rhabdomyolysis, liver toxicity