antidyslipidemic drugs
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| Ezetimibe (Zetia) | selectively inhibits intestinal absorption of cholesterol (inhibits more than >50% of absorption); lowers LDL by 15-20% but NO EFFECT on triglycerides
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| Ezetimibe (Zetia) monotherapy dose | 10 mg daily
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| % increase in cholesterol lowering by adding ezetimibe to statins | 15-20% greater lowering of cholesterol; reduction to 60% with 10 mg ezetimibe + 80 mg simvastatin
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| Ezetimibe (Zetia)'s only drug interaction | : bile acid resins inhibit absorption & action – thus, do not administer together (space apart)
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| high EPA/AA ratios (high fish oil) leds to increases in these plasma lipids | 3-series PGs and TX, 5-series LTs
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| high EPA/AA ratios (high fish oil) leds to decreases in these plasma lipids | 2-series PGs and TX, 4-series LTs
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| only FDA approved EPA/DHA (fish oil) supplement | Lovaza (formerly Omacor) from Reliant
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| TG level required in Lovaza's indication | >500 mg/dL
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| Lovaza dosage form (total; EPA; DHA) | 1 g capsules containing ~465 mg EPA & 375 mg DHA
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| Lovaza daily dosage | 4 g daily (combined EPA + DHA)
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| Lovaza SEs and interactions | mainly dyspepsia, loose stools, fishy taste; caution w/anticoagulants, blood thinners (okay with aspirin)
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| what is the risk of rhabdomyolysis when combining Lovaza and statins | none
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| decreased risk of overall mortality and CV mortality when omega-3 increases | 23% decrease in overall mortality; 32% decrease in CV mortality
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| lovastatin, simvastatin, atorvastatin - CYP metabolism | CYP 3A4 metabolism
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| fluvastatin - CYP metabolism | 2C9
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| rosuvastatin - CYP metabolism | 2C9 & 2C19
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| pravastatin - CYP metabolism | NOT METABOLIZED BY CYP450s
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| what is the warning for Simvastatin (Zocor) – amiodarone (Cordarone) interaction? | increased risk of severe muscle injury at dose greater than 20 mg/daily simvastatin along with amiodarone (anti-arrhythmic)
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| which 2 statins do not need to be given at night (long-acting statins) | Atorvastatin & rosuvastatin
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| 1st OTC statin in world | (Simvastatin) Zocor Heart Pro – 10 mg
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| dose related statin efficacy (%s increase/decrease) | LDL - decreased by ~ 20 – 60%HDL - raised by ~ 5 - 8%TGs - decreased by ~ 10 – 25% (due to decreased VLDL synthesis)
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| Atorvastatin (lipitor) usual daily dose | 10-80 mg qd
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| Fluvastatin (Lescol) usual daily dose | 20 mg once - 40 mg bid
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| Lovastatin (Mevacor) usual daily dose | 20 - 80 mg once
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| Lovastatin ER (Altocor) usual daily dose | 20 - 60 mg once
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| Pravastatin (Pravachol) usual daily dose | 40 - 80 mg once
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| Rosuvastatin (Crestor) usual daily dose | 10 - 40 mg
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| Simvastatin (Zocor) usual daily dose | 20 - 80 mg
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| safest fibrate to use with statin | fenofibrate
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| % improvement in LDL by combining Statins + bile acid-binding resins | 20 - 30% greater decrease
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| when combining statins + Niacin, how must the statin dose be adjusted | need to cut statins to 1/4 of maxium (or risk increased chance of myopathy)
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| when combining statins + fibrate, how must the statin dose be adjusted | need to cut statins to 1/4 of maxium (or risk increased chance of myopathy)
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| MOA for Cholestyramine & Cholestipol | Bile Acid Sequestrants - inhibits reabsorption of bile acids; decreased hepatic cholesterol levels results in enhanced synthesis of LDL-R on liver cells; promotes clearance of LDL-C & VLDL remnants
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| Bile Acid Sequestrants - drug interactions | (Cholestyramine & Cholestipol) decrease absorption of fat-soluble vitamins; interfere with absorption of some anionic drugs (e.g. thiazides, warfarin, thyroxine, digoxin)
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| Cholestyramine & Cholestipol (Bile Acid Sequestrant) efficacy | 8-24% decrease in LDL-C; some increase in VLDL so avoid in ptns w/hyperTGs
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| gemfibrozil (Lopid), fenofibrate (TriCor) MOA | PPAR-alpha agonist --> results in lower TG levels (decrease 25-50%) and raising of HDL levels (up to 15%)
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| fibrate uses | hypertriglyceridemia, combined hyperlipidemia, hyperlipidemia with decreased HDL
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| Fenofibrate dosing | once daily
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| Gemfibrozil dosing | two times a day
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| fibrate interactions | protein binding displacement; displaces warfarin, sulfonylureas
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| fibrate adverse events | myositis and rhabdomyolysis; dose-related effects; bigger problem with gemfibrozil
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| Niacin (nicotinic acid) MOA and results | inhibits major source of FA for TG synthesis; results --> decrease TG levels (~ 50%), decrease LDL-C formation (~ 25% decrease), increasing HDL-C levels (~ 15-40%)
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| therapeutic doses of Niacin | 1500-3000mg/day
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| niacin metabolism associated with flushing | conjugative pathway with glycine to form nicotinuric acid; low affinity, high capacity
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| niacin metabolism associated with hepatotoxity | amidation pathway, producing pyrimidine metabolites; high affinity, low capacity
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| niacin form that causes the most flushing | immediate release niacin (niacor)
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| niacin form with less flushing; increased liver toxicity | Long-acting niacin – Slo-niacin (dietary supp)
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| niacin form with less flushing, less hepatoxicity | Niaspan (extended-release; prescription only)
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| statins that are prodrugs | simvastatin (Zocor), lovastatin (Mevacor); hydrolyzed in GI tract to active drug
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| statin MOA | inhibits conversion of HMG-CoA to mevalonic acid (HMG CoA reductase inhibitors)
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| statin efficacy for high TGs (and req'd dose) | High triglyceride levels (>250 mg/dl) are decreased 35-45% by highest doses of most potent statins (simvastatin & atorvastatin, 80 mg/day; rosuvastatin, 40 mg/day)
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