Antihyperlipidemic Drugs

Question 1

What are 5 risk factors of cardiovascular disease?

Answer 1

1. Hyperlipidemia
2. Cigarette smoking
3. HTN
4. Obesity
5. Diabetes

Question 2

What are the primary causes of hyperlipidemia?

Answer 2

• Monogenic diseases
• Genetic polymorphisms
• Gene-environment interactions

Question 3

What are the classifications of hyperlipidemia, lipid profile, and etiology

Answer 3

Question 4

What are 5 types of antihyperlipidemic drugs?

Answer 4

1. HMG-CoA reductase inhibitors
2. Niacin
3. Bile acid-binding resins
4. Fibrates
5. Cholesterol absorptions inhibitors

Question 5

Statins

Answer 5

Rosuvastatin, Atorvostatin, Simvastatin, Lovastatin, Pravastatin, Fluvastatin

MOA: competitive inhibitors of HMG-CoA reductase (first committed step of cholesterol biosynthesis) > upregulation of HMG-CoA reductase and LDL receptors: decrease LDL, TG and small increase HDL

CA: DOC for LDL reduction, reduce cardiovascular mortality; other effects are improve endothelial function, decrease platelet aggregations, stabilize atherosclerotic plaque, and reduce inflammation

AE: elevations of aminotransferase, myopathy, and rhabdomyolysis (can lead to myoglobinuria)

Monitoring: aminotransferase measured at baseline, 1-2 months, and then every 6 months; CK baseline then measured if muscle pain/weakness

TCo: pregnancy

Question 6

Niacin (nicotinic acid)

Answer 6

MOA: inhibits adenylyl cylcase in adipocytes > inhibition of hormone-sensitive lipase > decreased transport of FAs to liver > decreased liver TG synthesis; decrease catabolic rate for HDL: decrease VLDL and LDL, increase HDL

CA: most effect drug for raising HDL, useful in pts with hyperlipidemia and low HDL, often combined with statins

AE: intense cutaneous flush after each dose when drug started of increased dose (aspirin given to decrease flush), acanthosis nigricans, hepatotoxicity, hyperglycemia, elevated uric acid levels

Question 7

Fibrates

Answer 7

Gemfibrozil, Fenofibrate

MOA: activates peroxisome proliferator-activiated receptors-alpha (PPAR-alpha) primarily on liver and brown adipose tissue > decrease plasma TG (increase lipoprotein lipase and hepatic oxidation of fats, decrease apoC-III) and increase plasma HDL

CA: DOC in severe hypertriglyceridemia

AE: mild GI disturbances, myositis, lithiasis

TCo: Gemfibrozil inhibits hepatic uptake of statins increasing their concentration in plasma

Question 8

Bile Acid-Binding Resins

Answer 8

Cholestyramine, Colestipol, Colesevelam

MOA: bind anionic bile acids in intestinal lumen to prevent reabsorption > hepatocytes increase conversion of cholesterol to bile acids > decrease intracellular cholesterol > upregulation of LDL receptors in liver: decrease LDL, slight increase HDL

CA: DOC for pregnant women and children, in combination with statin/niacin

AE: GI adverse effects (fewer with Colesevelam), may increase TG

TCo: hypertryglyceridemia, reduce absorption of drugs and liposoluble vitamins

Question 9

Cholesterol Absorption Inhibitors

Answer 9

Ezetimibe

MOA: inhibits intestinal transport protein (NPC1L1) absorption of cholesterol and phytosterols > LDL receptor upregulation: decrease LDL

CA: combination with statins, or if pts can’t tolerate statins

AE: reversible impaired hepatic function, myositis

TCo: should not be given with bile-acid sequestrants