4-Hyperlipidemia – Flashcards
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| vLDL is made in____ |
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| Liver |
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| LDL is made____ |
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| from vLDL catabolism and cellular synthesis |
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| HDL is made in _____and ______ cells |
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| Hepatic and Intestinal cells |
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| Exogenous Lipid metabolism |
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| LPL converts Chylomicrons to Chylo remnants. (from foods) |
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| Endogenous Lipid Metabolism |
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| -vLDL converted to IDL then LDL. SOme LDL go to subendothelial space in arteries and are oxidized & taken up by macrophages to make foam cells. (from liver cells) |
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| HDL reverse Transport |
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| Excess cholesterol from peripheral tissues is removed and transportd bac to liver. -Starts at liver/small intestine w/ APO1. -MAcrophage takes excess cholesterol fromarteries -too much Chol in mac signals receptors -HDL/APO1 takes chol |
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| CAD(Coronary artery disease) |
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| Stable chol plaq in coronary artery -plaq can rupture -If muscle dies__>>>Heart attack |
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| Cerebrovascular Disease |
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| Chol plaq ruptures in cerebral artery casue stroke (permanant damage) -Or TIA(temporary) |
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| PAD (Peripheral Artery Disease) |
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| Blocked artery in leg -dificulty wlkng -slows wound healing bc bad circulatn |
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| HMG COA RED Inhibitors |
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| -Statins -Block convrsn of HMGCOA to mevalonic acid. |
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| STrongest statins....longest half lifes |
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| Crestor Lipitor (can be taken anytime of day) |
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| Pt renal impaired avoid this statin |
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| Pravastatin |
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| Very bad cyp3a4 intrxns |
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| Simvastatin (Take at night ) |
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| HMG COA intrxn [STATINS] |
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| -Azoles -AMlodipine -Gemfibrozil -Verapamil, Diltiazem -MAcrolides -Grapefruit |
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| HMG COA Adv effx [STATINS] |
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| -HA, GI, Fatigue,myalgia (can do myopathy,rhabdo) |
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| for HMG COA inhibs LFTs and CKs |
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| AHA/ACC recommends agnst routine monitoring -LFT (ALT) baseline test recommended -CK evauated only for hi risk pt w/ muscle related side effx |
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| HMG Contra [STATINS] |
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| prego hep disease (LFTs >3xULN) rhabdo breast feed |
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| Cholesterol absorption INHIBITOR MOA |
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| -ZETIA(Ezetimibe) [well tolerated/no sidefx] -targets NPC1L1 protein. reduc absorp of cholesterol from the small intestines |
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| CHol absorp inhib RX intrxn |
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| BAS(bile acid seq)->tk Zetia 2 hrs before or 4 hrs aftr -cyclosporine -Fibrates(myopathy) |
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| Chol abs Inhib WARNINGS |
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| preg cat C elderly hep disease myopathy |
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| Chol ABs Inhib are considered similar to _____ |
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| Moderate dose statin |
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| Bile Acid Seqs and MOA |
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| -Cholestyramine(Questran) -Colestipol HCl(Colestid) -Colesevelam (Welchol) -MOA: prevents bile from small intest from going bac to liver. Depletes chol strg by forcing chol to be converted to more bile salt |
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| Triglycerides are inc as a result of what meds?` |
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| BAS(bile acid seq) |
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| BAS administer________ |
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| 2 hrs before or 4 hrs after any other med (not signifcntly absrbd..excreted in feces) |
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| Drug INTRXN BAS |
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| -Fat solble vitamins -B-blokcrs -Warfrin -Thiazide Diuretics |
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| BAS Adverse FX |
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| -GI constipation!!! -bloat, nasuea,flatuence -Inc triglyc (caution if TG>300) -inc bleeding in Vit K def pts |
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| Nicotinic Acids and MOA |
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| Niacin(reg release),NIASPAN(ext release) MOA:inhibits fat from making fatty acid to be turned into TG |
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| Nicotinic Acids RX intrxn |
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| Alcohol(flushing) BAS(Niacin dec) Warfrn(inc INR) |
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| Nicotinic Acids SIDE FX |
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| -Flushing/warm feeling -GI-NVD -Hyperglycemia (be careful w/DM pt) -Hepatotoxic or Hyperuricemia |
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| Dec flushing from niacin by____ |
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| giving Aspirin 1/2 to 1 hr before administration of niacin |
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| Nicotinic Acids Contraindications |
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| -Hep disease -Arterial Bleeding -Active peptic ulcer __---DISCONTINUE(AFIB,AST/ALT>2-3ULN,Acute gout,AB pain unexplained,Perisitent Hyperglyc) |
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| Most efective in HDL level inc (15-35%) |
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| Nicotinic Acids |
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| Fibric Acid Derivatives and MOA |
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| -Fenofibrate,Gemfibrozil MOA: activates PPARs to enhace lipoprotein lipase act & inc TG rich protein breakdwn.(reduces Hepatic vLDL) |
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| Fenofibrate ______but Gemfibrozil doesnt |
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| Decreases LDL |
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| Fibric Acid Derivatives require _____adj |
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| renal adjustment (metab thru glucuronidation) |
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| Fibric Acid Derivatives INTRXN RXs |
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| -Statins(especlly Gemfibrozil) -->RHABDO -BAS(dec absrp of fibrates) -WRFRN(inc INR) |
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| Fibric Acid Derivatives |
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| -well tolrtd -NVD -Risk of Rhabdo&Myopathy |
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| Fibric Acid Derivatives CONTRaINdication |
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| Active Liver Disease,gall bladder dis,biliary cirhosis -renal failure/dialysis |
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| OMEGA 3 FATTY ACIDS and MOA |
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| LOVAZA(EPA 465mg&DHA375mg) VASCEPA(EPA 1000mg) MOA: not completely defined,,,may reduce hepatic synth of TG |
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| OMEGA 3 FATTY ACIDS may inc________ |
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| LDL up to 45% with LOVAZA due to DHA (has not been studied w/ renal.hep impairment) |
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| OMEGA 3 FATTY ACIDS INTRXN & Side fx |
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| Warfarin--inc INR SIDE FX-Nausea,burp,fish breath/taste,prolong bleeding |
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| PCSK9 Inhibitors & MOA: |
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Alirocumab(q 2 weeks SQ) Evolocumab (q 2 weeks SQ) MOA:-monoclonal antibodies bind PCSK9 -inc Hepatic LDL receptors. [PCSK9promotes degradation of LDL receptors] |
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| PCSK9 inhib indications |
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| Familial hypercholesteremia in addition to diet and max tolerated statin therapy WARNING:sensitivity(expensive) |
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| MTP inhibitor |
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| -Lomitapide(juxtapid) -Inhibits MTP,prevents formation of apoB containinglipoproteins in enterocytes & hepatocytes -reduces chylo&vLDL formation Indicated for familial hypercholesteremia |
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| MTP inhibitor Adverse effx |
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| Adverse Reactions: NVD,ab pain fatigue/dizzy hepatic---steatoosis&liver transaminases inc >3xULN |
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| Dose limit w/ Clarithromycin and Atorvastatin |
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| Atorvastatin dose limt to 20mg/D |
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| GRAPEFRUIT JUICE LIMIT WITH STATINS |
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| 1.2L/DAY GRAPEFRUIT WITH STATINS CANNOT TAKE GRAPEFRUIT W/ lova or simvaSTATIN!!!!! |
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| CANNOT TAKE GRAPEFRUIT W/ |
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| LOVA or SIMVASTATIN |
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| CHD Prevention strategies |
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| smoke cessat BP reduc Psycosocial weight loss nutrition physical act(30-60mins 5-6 days/wk) |
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| Metabolic syndrome--->>>>CV RISK CONTRIBUTIONS (3/5 OF FOLLOWING) |
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| -HDl <50(women) <40(men) -Trigllycerides>/= 150mg/dL -Glucose>/= 100mg/dL -Waist circumf>/= 35 inches(men,,,30(women) -BP >/= 130/85mmHg |
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| Metabolic syndrome more common in_______ |
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| Women---Afric-Amer,Hispanics |
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| Recheck Lipid profile q 5 yrs if normal in |
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| men>40yrs women>50yrs |
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| Friedewald equation for LDL-C |
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| LDL=TC-(HDL+TG/5) |
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| Friedewald Equation for TC |
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| TC=LDL+(HDL+TG/5) |
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| Friedewald for NON HDL |
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| NON HDL=TG/5+LDL or TC-HDL |
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| Secondary causes of Lipid Abnormalities |
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| Diet,Drugs,Diseases.Disordersof altred metab(preg,obese,hypothyroid) |
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| Benefits Exceed risks for initiating STATIN in Group 1 |
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| Pt w/ [w/o NYHA class II-IV HF or hemodialysis pt] -ASCVD -ACS or MI Hx -Stable/unstable Angina -Coronary/arterial revascularization -Stroke,TIA, or PAD |
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| Benefits Exceed risks for initiating STATIN in Group 2 |
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| pt w/ LDL-C>/= 190mg/dL |
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| Benefits Exceed risks for initiating STATIN in Group 3 |
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| 40-75yrs w/ DIABETS and LDL-C 70-189mg/dL w/o clinical ASCVD |
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| Benefits Exceed risks for initiating STATIN in Group 4 |
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| 40-75yrs w/o diabetes or ASCVD -LDL-C 70-189mg/dL & estimated 10 yr ASVD risk of 7.5% or higher |
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| High dose statins lower LDL by |
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| >/= 50% |
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| Moderate dose statins lower LDL by |
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| 30-<50% |
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| Grp(1) STATIN initiation Tx </=75yrs w/ CLinical ASCVD |
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| Hi intensity statin (mod statin if not candidate) |
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| Grp(1) STATIN initiation Tx >75 yrs w/ Clinical ASCVD |
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| Mod intensity statin |
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| Grp(2) STATIN initiation Tx LDL-C >/=190mg/dL |
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| Hi intensity statin (mod if not candidate) |
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| Grp(3) STATIN initiation Tx Diabetes w/ LDL-C 70-189mg/dL Age 40-75yrs |
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| Mod intensity statin |
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| Grp(3) STATIN initiation Tx Diabetes w/ LDL-C 70-189mg/dL Age 40-75yrs w/ estimated 10yr ASCVD risk >/=7.5% |
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| Hi intensity statin |
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| High Intensity Statin Therapy |
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| atorvastatin 40-80 mg •rosuvastatin 20-40 mg |
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| Moderate Intensity Statin Therapy |
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| •Atorvastatin 10 (20) mg •Rosuvastatin(5) 10mg •Simvastatin 20-40mg •Pravastatin 40 (80) mg •Lovastatin 40mg •FluvastatinXL 80mg •Fluvastatin40mg bid •Pitavastatin2-4mg |
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| Low Intensity Statin Therapy |
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| •Simvastatin 10 mg •Pravastatin 10-20 mg •Lovastatin 20 mg •Fluvastatin20-40 mg •Pitavastatin1 mg |
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| FibricAcids: Place in therapy ----Caution when initiating gemfibriozilin patient on statin,WHY??? |
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| –increased risk for muscle symptoms |
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| Consider fenofibratein combo with low or moderate intensity statin WHEN???? |
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| when TG ? 500 mg/dl |
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| Decreasing the statin dose maybe considered when..... |
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| 2 consecutive values of LDL are < 40 mg/dl |
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| If pt on STATIN develops DM is this a reason to stop STATIN Tx? |
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| NO not an indication to stop statin |
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| PREGO WARNING w/ STATINS |
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| should be D/C if pregnant and D/C 2-3 mobefore getting pregnant. Resume post pregnancy. |
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| Fasting lipids panel within ______weeks after initiation or dose adjustment of statin |
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| 4-12 weeks (Fasting lipid panel every 3-12 months after dose stable) |
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| SIMVASTATIN dose Patients taking diltiazem or verapamil |
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| 5-10mg |
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| SIMVASTATIN dose amlodipineor ranolazine– |
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| 5-20mg |
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| Statins significantly metab by CYP3A4 |
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| -Lova -Atorv -Simva |
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| Statins significantly metab by 2C9 |
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| Fluvastatin |
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| Statins NOT significantly metab by CYP450 |
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| Prava Rosuva Pitava |
