Anti-hyperlipidemics (exam 2)

Question 1

Nicotinic acid, Niacin (Vitamin B3)

Answer 1

-decreases lipolysis activity in adipose tissue
-increases lipoprotein lipases activity in the liver, decreasing TG and VLDL synthesis
-lipolipase activity in plasma increases removal
-USES: decrease TGs, cholesterol (VLDL, LDL, IDL) and increases HDL
TOX: red flush, pruritis, neovascular disease, contraindicates anti-HTN agents, increases hyperuricemia
Ocular toxicity of cystoid macular edema and toxic amblyopia

Question 2

Clofibrate (Atromid-S)

Answer 2

-fibric acid derative; fibric acids might bind to PPAR receptor, which may regulate lipid enzyme transcription
-increase lipoprotein lipase activity
-aid entry of TG to peripheral tissue
USES: decreases VLDL, TGs, LDL, cholesterol, and increases HDL
-MOST USEFUL IN HYPERTRIGLYCERIDEMIA
TOX: liver cancer (in animal studies), increase non-CV deaths, anemia/leukopenia, increased gall stones (increased cholesterol excretion), nausea diarrhea, weight gain, increses effets of oral anti-coagulants (warfarin)

Question 3

Gemfibrozil (Lopid)

Answer 3

• fibric acid derivative
• increases peripheral lipolysis activity; decreases TGs and VLDL while increasing HDL
• very useful in hypertriglyceridemia
• TOX: GI upset, thrombocytopenia, leukopemia, anemia; blurred vision, muscle/abdominal pain, increases effects of Vit K anti-coagulents, gall stones and liver dysfunction

Question 4

Fenofibrate (Tricor)

Answer 4

• fibric-acid derivative
• acts to incresae lipoprotein lipase, increase HDL decrease TGs/LDL
• TOX: hepatitis, pancreatitis, myopathy, abdominal pain (greatest risk of the fibric acids)
• much bigger risk when used with statins+niacin

Question 5

Cholestryamine (Questran)

Colestipol (Colestid)

Answer 5

-Bile acid binding resins
-oral admin, but it is never absorbed; acts to bind fats, and then get excreted in feces
-binds bile acids in the gut, prevent reabsorption of bile acids and cholesterol
-forces body to metabolize cholesterol to bile acids, decreases LDL and cholesterol from plasma
-ion exchange of CL- for bile acid
-Best used for high cholesterol patients
-TOX: taste/nausea, GIT upset/constipation, increases TGs (NOT good for hypertriglyceridemia)
Drug contra: digoxin, thiazide diuretics, Vit K absorption decreased

Question 6

Lovastatin (mevacor)
Simvastatin (zocor)
Pravastatin (Pravachol)
Fluvastatin (lescol)
Atorvastatin (Lipitor)
Rosuvastatin (crestor)

Answer 6

-HMG-CoA reductase inhibitors
-HMG0CoA reductase is rate limiting enzyme in cholesterol synthesis
-Body will increase HMG-CoA reductase synthesis, returns to normal, but this synthesis increases LDL receptors and increases removal of LDL/cholesteror
USES: high cholesterol states (not TGs), works with niacin and resins (more toxic though); use only after diet fails
TOX: well tolerated, but headache, GIT distress, rash; placebo muscle pain?
-must monitor liver for changes
-myopathy and rhabdomyolysis (breakdown of muscle proteins, fatal, increased with niacin/fibric acids)
-CATARACTS must be monitored (higher incidence with diabetes-1)
-contraindicated in pregnancy, fetus needs cholesterol

Question 7

Ezetimibe (Zetia, Vytorin-combo with statin)

Answer 7

• intestinal sterol absorption inhibitor; blocks intestinal transport protein NPC1L1, used in cholesterol absorption
• upregulates LDL receptors on hepatocytes, increases LDL removal from plasma
• USES: decreases LDL, doesn’t change HDL much; when used with statins, further increases LDL
• controversy: Vytorin combo (statin+ezetimibe) showed no effect over statin alone
• TOX: minimal, 1% headache/diarrhea; infrequent myalgia and altered liver fxn