Pharm: Lipid Lowering Agents

Question 1

Statins

Answer 1

lovastatin, pravastatin, etc.
HMG-CoA reductase inhibitors
inhibits conversion of HMG-CoA to cholesterol precursor mavelonate --> v cholesterol synthesis by liver --> ^ LDL receptor expression on hepatocytes --> v LDL in circulation
**v mortality in CAD patients
vvv LDL
^ HDL
v TG (VLDL and CHY)
Side effects: hepatotoxicity (^LFTs), myopathy (esp w fibrates or niacin)

Question 2

Bile Acid Resins

Answer 2

cholestyramine, colestipol, colesevelam
Prevents intestinal reabsorption of bile acids –> liver must use cholesterol to make more: ^ activity of HNG-CoA reductase and LDL receptor
vv LDL
slight ^ HDL
slight ^ TG (VLDL) *don’t use in patients with hypertriglyceremia
Side effects: GI upset, v absorption of other drugs and fat-soluble vitamins (A, D, E, K), gallstones

Question 3

Ezetimibe

Answer 3

Prevents cholesterol absorption at small intestine brush border –> CHYs have v cholesterol –> v exogenous CHY to liver –> ^ activity of HMG-CoA reductase and ^ LDL receptor
vv LDL
no change to HDL and TGs
Side effects: rare ^ LFTFs, diarrhea

Question 4

Fibrates

Answer 4

Gemfibrozil, bezafibrate, fenofibrate
Upregulates LPL –> activates PPAR-alpha –> HDL synthesis –> ^ TG clearance
v LDL
^ HDL
vvv TG
Side effects: myopathy (^ risk w statins), cholesterol gallstones

Question 5

Niacin (vitamin B3)

Answer 5

Inhibits lipolysis (hormone sensitive lipase) in adipose tissue
v hepatic VLDL synthesis –> v TG
vv LDL
^^ HDL (v HDL cholesterol transfer and delays HDL clearance)
v TG
Side effects: red, flushed face (mediated by PGEs), which is v by NSAIDs or long-term use; hyperglycemia, hyperuricemia (–> gout)