cholesterol ---(CYP7A1)---> bile acids (upregulated when cholesterol is high to reduce the level of cholesterol in hepatocytes, or when bile acids are low)
Cholestyramine
Bile acid (BA) sequestrant. Complexes bile salts (BS)-->prevent recycling of BAs from GI-->dec BA levels in circulation-->dec inhib of CYP7A1-->inc synthesis of new BSs-->dec liver chol --> inc LDL receptors (to make more chol) --> dec LDL in plasma
Colestipol
Bile acid (BA) sequestrant. Complexes bile salts (BS)-->prevent recycling of BAs from GI-->dec BA levels in circulation-->dec inhib of CYP7A1-->inc synthesis of new BSs-->dec liver chol --> inc LDL receptors (to make more chol) --> dec LDL in plasma
When would you NOT use bile acid sequestrants?
in hypertriglyceridemias because they inc VLDL and TG's
Adverse effects of bile acid sequestrants
1. bloating, 2. constipation
Drug interactions of bile acid sequestrants
Dec absorption of digoxin, thiazides, tetracyclines, warfarin, and vitamin K.
What is HMG CoA Reductase?
Rate limiting enzyme in the synthesis of cholesterol
What are statins?
Inhibit HMG-CoA Reductase --> decrease synthesis of cholesterol in liver --> inc LDL receptors --> dec LDL in circulation & dec hepatic synthesis of VLDL and ApoB
What is the effect of statins on HDL and TG's?
small inc in HDL and small dec in TG's (atorvostatin)
What is the effect of statins on vessels?
Inc in NO (vasodilator) and decreases mRNA for endothelin-1 (vasoconstrictor)
