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PCol I - Exam 4

antidyslipidemic drugs

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