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80 Cards in this Set
- Front
- Back
What is hyperlipidemia?
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Increase in plasma cholesterol, liproteins, triglycerides or a combination.
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Hyperlipidemia puts you at a risk for what heart disease?
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CAD
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What are the 5 classes of anti-hyperlipidemics?
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1. HMG-CoA Reductase Inhibitors (Statins)
2. Bile Acid Sequestrants 3. Cholesterol Absorption Inhibitors 4. PPAR-alpha Activators (Fibrates) 5. Miscellaneous |
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Name 7 HMG-CoA Reductase inhibitors
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Pitavastatin, Rosuvastatin, Atorvastatin, Simvastatin, Lovastatin, Pravastatin, Fluvastatin
"Pit a Rose At Simva's Love -- Prada Flu" |
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Which 2 HMG-Coa Reductase inhibitors are prodrugs?
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Lovastatin & Simvastatin
(Love Simva, the pro) |
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MOA of HMG-CoA reductase inhibitors?
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competitively inhibit HMG-CoA reductase, which is the rate limiting step in making cholesterol. Up regulates LDL-C receptors & increases lipid metabolism
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What are Statins' lipoprotein effects?
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Most potent choleterol effector by reducing LDL & TG, and raising HDL.
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What are the potency relationships between the Statin drugs?
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Pitavastatin (2mg), Rosuvastatin (5mg), Atorvastatin (10mg), Simvastatin (20mg), Lovastatin/Pravastatin (40mg), Fluvastatin (80mg)
"Pit a Rose at Simva's Love -- Prada Flu" |
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Adverse effects of Statins?
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Muscle & Liver!
AST/ALT elevations, myopathy |
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Drug-drug interactions of Statins
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CYP3A4/2C9 inhibitors (Lova/Simva pro drugs)
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Contraindications for STATINS?
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Liver & Renal failure, Pregnancy
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Name 3 Bile Acid sequestrants
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Cholestyramine, Colestipol, Colesevelam
CholestyraMINE is powder like MINING power. ColestipOl has O for Oral granules & tablets. Colesevelam is a tablet. |
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MOA of bile acid sequestrants
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non-absorbable anion-exchange resin/polymers, binds bile acids in intestinal lumen, upregulation of LDL-C receptors, and cholesterol 7-aplha hydroxtlase
Overall reduces LDL. |
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What state/form of drugs is especially susceptible to drug-drug interactions?
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prodrugs
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True or False. The higher the anti-hyperlipidemic drug the greater the effect.
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False. Doesn't always correlate.
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What is the rate-limiting step in formation of cholesterol?
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HMG-CoA reductase
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True or False. If I raise the dose of Fluvastatin from 40 mg to 80 mg I can expect a proportional drop in cholesterol.
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FALSE... see slide titled "majority of LDL-C lowering occurs at the LOWEST-statin dose
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What are the two major AE's of pretty much all anti-hyperlipedemics?
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MUSCLE AND LIVER
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You put a pt. on Lovastatin. 2 weeks later they come in and say "i feel like i have the flu!". What lab should you (have been) monitoring?
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CK for myopathy! (An important AE is myopathy)
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Before you get into a "statin cocktail" with a patient what baseline labs should you probably order?
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AST/ALT, and CK
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What is the MOA of cholestryamine?
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non-absorbabale anion-exchange resins/polymers bind bile acids in intestinal lumen. this results in upregulation of LDL-C receptors and cholesterol 7-alpha hydroxlyase
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Hypercholesterol pt. has a major problem w/ low HDL and high TG. What drug do you NEVER choose as monotherapy in this case?
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Bile Acid sequestrants
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You're taking a med history of a pt. you saw a couple months ago. They say, "well i've been taking my colestipol, antacid, and my other meds in the morning w/ breakfast." What are they doing wrong?
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Don't take bile acid sequestrants or antacids w/ any other drugs!
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If you realllly need to raise HDL in your pt., (their level for HDL is 21) what is the target drug to add to the statin?
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Niacin (potent inc. in HDL)
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Pt. is taking 1000 mg of Niacin. What is the biggest AE? How can you prevent it?
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cutaneous flushing (cherry red); prevent by starting low (even though its ineffective at first) and take an ASA before taking niacin
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Pt. has gout or diabetes. What anti-hyperlipidemic do you avoid?
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niacin (elevates serum glucose and uric acid)
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Pt. primarily has hypertriglyceridemia problem. What is your DOC?
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Fibrates (PPAR-alpha activators)
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What lipoproteins have high TG's?
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chylomicrons and VLDL
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What lipoprotein has the most protein content (opposed to lipid)
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HDL
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What does the LCAT do?
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It esterifies the cholesterol in HDL so HDL becomes spherical
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What is the apoprotein for chylomicrons?
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apo B48
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What is the apoprotein for VLDL?
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apo B100
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VLDL carries ?
LDL carries ? |
VLDL- TG's; LDL- cholesterol esters
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What is the MOA of lovastatin?
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competitively inhibits HMG-Coa Reductase
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LPL (lipoprotein lipase) is on the surface of the endothelium of capillaries in what parts of the body?
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capillaries of adipose tissue, skeletal muscle, and smooth muscle
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In what tissues is Km of LPL high? Low?
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high in adipose tissue, low in cardiac and skeletal muscle
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Where is the apo B100 made?
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Liver
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In the blood, what are FA's bound to (when not free)?
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albumin
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What is the common intermediate of triacylglycerol formation in adipose tissue and the liver?
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phosphatidic acid
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A critical functional protein, MTP, is missing in what disease? (the result is inability for form VLDL and chylomicrons)
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Abetalipoproteinemia
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Exogenous trigylcerides are carried by what? Endogenous?
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Exo: chylomicrons; Endo: VLDL
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What apoprotein activates LPL?
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CII
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What apoprotein helps chylomicron remnants get taken up by the liver?
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apoE
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What apoproteins are associated with HDL?
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A (I & II) and carries CII and E to other lipoproteins
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What is the function of CETP?
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An enzyme found in HDL. It transfers cholesterol ester from HDL to VLDL and takes TG from VLDL converting it to LDL
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What is defective in familial hypercholesterolemia?
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LDL receptor
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What is wrong in type II hyperlipidemia?
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Lack of functional LDL receptors
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What is wrong in cholesterol ester storage disease?
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Decreased activity of lysosomal esterase (acid lipase)
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What goes wrong in Wolman’s Disease
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Absence of lysosomal esterase
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Characteristics of Alpha-lipoprotein deficiency?
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– Decreased HDL
– VLDL and LDL may be decreased – Deposition of cholesterol esters in RES – Defective ABC1 |
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Characteristics of Lecithin-Cholesterol Acyltransferase Deficiency?
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– Decreased esterification of cholesterol
– Decreased LDL and HDL – Increased VLDL and chylomicrons – Foam cells in bone marrow and kidneys |
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Big one. What are the characteristics of the types of hyperlipoproteinemias?
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– Type I = Presence of chylomicrons (Increased
triglyceride) – Type IIa = Increased LDL (Increased cholesterol) – Type IIb = Increased LDL and VLDL (Increased cholesterol and triglyceride) – Type III = Increased IDL (Increased cholesterol and triglyceride) – Type IV = Increased VLDL (Increased triglyceride) – Type V = Increased VLDL and presence of chylomicrons (Increased triglyceride) |
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What is the primary means of clearance of HDL from the blood?
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Uptake by the liver and other tissues via scavenger receptor SR-B1
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What are the 2 types of local therapy for hypercholesterolemia?
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Bile acid sequestrates & cholesterol absorption inhibitors
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What are AE of bile acid sequestrants?
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GI, liver enzyme elevation, pancreatitis, bledding/hypothrombinemia (messes up vit K absorption)
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What vitamins should not be taken with bile acid sequestrants bc of drug durg interactions?
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Fat soluble - vit A, D, E, K
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When should pts take drugs that interact with their hyperlipidemia drugs?
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1-2 hrs before or 2-4 hrs after
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If a pregnant lady has to take a bile acid sequestrant, which one should it be?
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Colesevelam (B)
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MOA of Niacin (nicotinic acid)
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reduces cellular/enzymatic hepatic synthesis of TG, VLDL-C and LDL-C, increases LDL-C receptor activity, and decreases HDL-C catabolism.
Better than Statins at giving an HDL boost. |
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What are the AE of Niacin (nicotinic acid)?
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1. Cutaneous FLUSHING (prevent by taking ASA 30-40 min before, start with low dose & titrate up)
2. GI stress 3. elevated serum glucose - don't give to Diabetics 4. elevation of serum uric acid - Gout 5. myopathy 6. AST/ALT elevation 3x |
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Contraindications for Niacin?
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chronic liver/gallbrallder disease, sever gout, peptic ulcer disease, diabetes, bleeding disorders (on Warfarin), pregnancy (C)
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Name 2 PPAR-alpha- activators "fibrates"
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Fenofibrate (prodrug) and Gemfibrozil
"Fibrates are Fine Gems" |
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MOA of fibrates?
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Activate PPARs which transcribe genes involved in lipoprotein metabolism.
Best at reducing TG |
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AE o"Ef fibrates?
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AST/ALT elevation, myopathy, predisposition to gallstones
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Contraindications of fibrates?
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severe renal/hepatic disease, biliary cirrhosis,/cholelithiasis, pregnancy (C)
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Name 1 cholesterol absorption inhibitor
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Ezetimibe
"Ezet is Timid and inhibits cholesterol absorption" |
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MOA of Ezetimibe
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selectively inhibits at the brush border of the small intestine the absorption of cholesterol & phytosterols
Never use as 1st DOC |
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AE of Ezetimibe
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GI - diarrhea, abdominal pain/fatigue/back pain, increased AST/ALT, myopathy
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Contraindications of Ezetimibe
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Severe hepatic disease, pregnancy (C)
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Name 1 miscellaneous agent against hypercholesterolemia
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Fish Oil (omega-3 FA, EPA, DHA & ALA)
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Name an FDA approved miscellaneous agent
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Lovaza - ethyl esters formulation
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What is TLC and how does it relate to drug theraphy?
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Therapeutic Lifestyle Changes. Drug theraphy is always ADDED to TLC; it NEVER replaces it!
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What class of agents has the greatest potential to have the greatest TG lowering effect?
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Firbrates - Fenofibrate or Gemfibrozil
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What 1 negative lipid effect is possible with the class of fibrates?
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Can potentially increase LDL-C by 5-20% in some pts
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What class of agents has the greatest potential to have the greatest HDL-C raising effect?
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Niacin (nicotinic acid)
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What patients should not get niacin?
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Those with chronic liver/gallbadder disease, gout, peptic ulcer disease, diabetes, bleeding disorders, and preganancy
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What type of patients should not get the cholesterol absoprtion inhibitor, Ezetimibe?
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those with severe hepatic disease or pregnant women
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What 3 lipid lowering drugs are prodrugs?
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Lovastatin, Simvastatin, and FenoFibrate
"Love a Fine Simva" |
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What patients should not get a bile acid sequestrant?
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people with hypertriglyceridemia (high TGs), dysbetalipoproteinemia, ileus/GI obstruction, dysphagia, advanced renal disease bc of Cl balance, and pregnant women
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If you have a hypercholesterolemic pt or a young female who is hypercholererolemic who desires to have a child, what drug class is the best choice (carries the least risk)?
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Give local theraphy with a bile acid sequestrant - Colesevelam and possible Fish Oil
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