Kaplan Section 3 Chapter 7 Anti-Hyperlipidemics
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| What is 7-a-hydroxylase (CYP7A1)? | cholesterol ---(CYP7A1)---> bile acids (upregulated when cholesterol is high to reduce the level of cholesterol in hepatocytes, or when bile acids are low)
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| 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
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| 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
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| When would you NOT use bile acid sequestrants? | in hypertriglyceridemias because they inc VLDL and TG's
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| Adverse effects of bile acid sequestrants | 1. bloating, 2. constipation
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| Drug interactions of bile acid sequestrants | Dec absorption of digoxin, thiazides, tetracyclines, warfarin, and vitamin K.
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| What is HMG CoA Reductase? | Rate limiting enzyme in the synthesis of cholesterol
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| 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
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| What is the effect of statins on HDL and TG's? | small inc in HDL and small dec in TG's (atorvostatin)
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| What is the effect of statins on vessels? | Inc in NO (vasodilator) and decreases mRNA for endothelin-1 (vasoconstrictor)
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| Adverse effects of statins | 1. Diarrhea, 2. Myalgia/myopathy (watch CK), 3. rhabdomyolysis (gemfibrozil, nicotinic acid), 4. inc LFT's
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| What is nicotinic acid? | anti-hyperlipidemic. 1. inhib VLDL and apoprotein synthesis in hepatocytes, 2. inc HDL --> dec plasma VLDL, LDL, and TG's, 3. activates lipoprotein lipases, 4. inc tPA, 5. dec serum fibrinogen
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| Adverse effects of nicotinic acid | 1. flushing, 2. pruritis (use ASA), 3. rashes, 4. hyperuricemia, 5. hyperglycemia, 6. hepatotoxicity, 7. GI ulcer exacerbation.
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| Gemfibrozil | anti-hyperlipidemic. 1. activates lipoprotein lipases --> inc catabolism of VLDL and LDL, 2. dec plasma VLDL, TG's, LDL, 3. small inc in HDL
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| Adverse effects of gemfibrozil | 1. GI distress, 2. rash, 3. gallstones, 4. hypoK, 5. myositis
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| Drug interactions of gemfibrozil | potentiates warfarin and sylfonylurea hypoglycemics
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| Ezetimibe | anti-hyperlipidemic. 1. prevents intestinal absorption of cholesterol (used with statin to dec LDL)
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| Adverse effects of ezetimbe | GI distress
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