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69 Cards in this Set
- Front
- Back
What are the two conditions that are the exception to the rule of attempting to control hyperlipoproteinemia by dietary management before using drugs?
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familial hypercholesterolemia
and familial combined hyperlipidemia |
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What diet is recommended for total fat intake?
low saturated fat intake? cholesterol intake? |
<30% total fat calories
<7% low saturated fat <200 mg cholesterol = 10-20% reduction in serum cholesterol |
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Name three foods that may reduce LDL?
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oat
rice bran soy (LDL and cholesterol) |
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___ reduce triglyceride levels
___ increase triglyceride levels |
omega-3- fatty acids reduce
omega-6- fatty acids increase |
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Name two dietary supplements that inhibit HMG-CoA reductase?
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Cholestin and Evolve
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Name two bile acid binding resins
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cholestyramine and colestipol
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What is the primary aim of cholestyramine and colestipol?
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to lower blood cholesterol - especially LDL
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Name two indications for cholestyramine and colestipol
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HETEROZYGOUS familial hypercholesterolemia
and combined hyperlipidemia |
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What is the primary action of cholestyramine and colestipol?
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nonspecifically binds bile acids within the intestinal lumen; inhibits the reabsorption of bile acid
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What is the secondary action of chlestyramine and colestipol?
(6 steps) |
1. cholesterol is the precursor of bile acid -> inhibition of bile reabsorption causes increased channeling of cholesterol to the production of bile acids
-> 2. decreased intra-hepatic cholesterol level -> 3. up-regulation of ApoB and ApoE receptors on hepatocytes -> 4. INCREASED clearance of lipoproteins LDL, IDL, and maybe VLDL -> 5. ADVERSE effect of reduced intra-hepatic cholesterol -> increased secondary cholesterol production -> 6. constipation, bloating, gallstones, steatorrhea |
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Name five drug interactions of cholestyramine and colestipol?
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digitalis preparations
thiazide diuretics beta blockers warfarin fat soluble vitamins (esp K) |
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How do you manage those drug interactions?
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take cholestyramine and colestipol with or just before meals
take other drugs 2 hours before the resins or 4 hours after the resins (cholestyramine and colestipol) |
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cholestyramine and colestipol decreased LDL cholesterol by ...
increased HDL cholesterol by... and are often given together with... |
decrease LDL 15-30%
increase HDL 3-5% given with HMG-CoA reductase inhibitors |
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3-hydroxy-3-methylglutaryl coenzyme A
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HMG-CoA
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Name two indications for HMG-CoA reductase inhibitors
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familial hypercholesterolemia
and combined hyperlipidemia |
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HMG-CoA reductase inhibitors are also known as...
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statins
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What is the primary MOA of a statin?
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inhibit HMG-CoA reductase
a key enzyme in cholesterol synthesis in the liver |
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What is the secondary action of statins?
(3 steps plus 1 other effect) |
inhibit the cholesterol synthesis enzyme -?
1. reduced intrahepatic cholesterol -> 2. 180% upregulation of ApoB and ApoE receptors -> 3. increased clearance of ApoB and ApoE containing lipoproteins (LDL, IDL, VLDL) and increase HDL |
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statins can lower triglyceride levels up to...
can lower LDL levels by... can increase HDL levels by... |
25% decreased triglycerides
40% decreased LDL 15% increased HDL |
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Why are statins given in the evening?
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the diurnal pattern of cholesterol biosynthesis
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How do you prescribe a statin to a patient with hepatic parenchymal disease and why?
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mild hepatotoxicity ->
indicated by increased serum aminotransferase levels -> therefore give reduced dosage |
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What finding is increased when a patient on a statin is also on cyclosporin or fibric acid derivatives?
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myopathy - reversible upon cessation of therapy
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Name four psychiatric symptoms associated with statins?
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anxiety
depression obsessions delusions |
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What about statins and pregnant women?
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Never give a statin to a pregnant woman!
only give to women of childbearing age when they are highly unlikley to conceive |
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Do statins have any benefit to healthy middle-aged men and women with near NORMAL levels of blood cholesterol?
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can reduce risk of heart attacks and stroke by 30%
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Grapefruit juice and verapamil can significantly increase the serum concentraions of which three statins by inhibiting which CYP enzyme?
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lovastatin
simvastatin atorvastatin CYP3A4 |
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What does grapefruit juice and verapamil do to pravastatin and fluvastatin?
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nothing
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first statin approved by FDA
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lovastatin
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lovastatin is an inactive ___ prodrug hydrolyzed in the GI tract to active ___ derivative
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lactone prodrug
beta-hydroxyl derivative |
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__% of lovastatin is absorbed from the GI tract...undergoes extensive first pass elimination and leaves less than ___% of orally administered dose to reach circulation?
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30% absorbed
5% reaches circulation |
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this statin was approved in 1996 and is given as an active drug...it is readily absorbed and is 2x more potent than lovastatin
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atorvastatin
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This drug is the most effective in reducing LDL (up to 60%) and triglycerides (up to 30%)
it also is the most effective in raising HDL levels |
atorvastatin
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This drug is similar to atorvastatin, was approved in 2004, and is rumored to have a higher incidence of rhabdomyolysis and renal failure
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rosuvastatin
(don't give more than 20 mg/day) |
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Estrogen replacement therapy increases the HDL cholesterol up to __% and decrease LDL __%
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15%
15% |
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What is the MOA for estrogen replacement therapy?
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unknown
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What does ezetimibe do?
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cholesterol absorption inhibitor --> acts on brush border of gut wall to prevent cholesterol absorption through villi
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What happens when you give ezetimibe with a statin?
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lower LDL additional 25%
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Name four classes of drugs that predominantly lower cholesterol
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1. bile acid binding resins (cholestyramine and colestipol)
2. HMG-CoA reductase inhibitors (statins) 3. Estrogen replacement therapy 4. cholesterol absorption inhibitor (ezetimibe) |
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trigylceride levels >400 mg.dl increase the risk of...
levels >100 mg/dl increase the risk of... |
heart disease
pancreatitis |
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Name five indications for niacin (nicotinic acid)
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1. heterozygous familial hypercholesterolemia
2. mixed lipemia 3. combined hyperlipoproteinemia 4. familial dysbetalipoproteinemia 5. Lp(a)hyperlipoproteinemia |
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What is the primary MOA of niacin?
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direct decrease in hepatic synthesis of VLDL
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What is the secondary MOA of niacin?
(one plus an extra) |
decreased VLDL ->
decreased IDL and LDL increases HDL MORE THAN ANY OTHER DRUG (up to 35%) -> decreasing Lp(a) levels |
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Name six side effects of niacin?
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1. flushes
2. pruritis 3. rashes 4. hyperuricemia 5. reversible carbohydrate tolerance impairment 6. rare hepatotoxicity |
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Name two fibric acid derivative drugs?
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gemfibrozile and fenofibrate
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Name two indications for fibric acid derivatives?
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familal hypertriglyceridemia
familial disbetalipoproteinemia |
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Name three MOAs of fibric acid derivatives?
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exact MOAS unknown but...
1. increases lipoprotein lipase activity (VLDL catabolism) 2. decreases VLDL synthesis and excretion by liver 3. increases HDL cholesterol |
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fibric acid derivatives (gemfibrozel and fenofibrate) decrease triglyceride by __%
increase HDL by __% and do what to LDL levels |
triglycerides down by 50%
HDL up by 15% LDL may go up or down |
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What is the most frequently used fibric acid derivative?
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gemfibrozil
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gemfibrozil is __ absorbed by GI tract
has half life of __ and excreted as ___ through kidneys |
readily absorbed
t1/2 = 90 minutes excreted as glucoronid conjugate through kidneys (therefore avoid in patients with kidney disease) |
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is gemfibrozil the active carboxylic acid form?
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yes
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Name five possible but rare side effects of gemfibrozil
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rash
GI sx myalgia anemia gallstones |
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gemfibrozil potentiates the action of which two drugs by displacing them from albumin?
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coumadin and indandione anticoagulants
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this fibric acid derivative is rarely used because of possible increase in malignancies and has pharmacokinetics and drug interactions are similar to gemfibrozil
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clofibrate
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this fibric acid derivatives is widely used in Europe
was recently approved in the USA and is similar to gemfibrozil |
fenofibrate
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consumption of large amounts of ___ by Alaskan natives reduced CHD mortality rate?
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fish oil containing omega-3 polyunsaturated fatty acids
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How does fish oil work?
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decreases triglyceride levels by suppression of VLDL production and increases HDL cholesterol
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What is the fish consumption advice?
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2 servings per week- especially fatty fish like salmon, tuna, mackerel, herring, and sardines
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Name the three classes of drugs that predominantly lower triglyceride
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niacin
fibric acid derivatives (gemfibrozil, fenofibrate, clofibrate) fish oil |
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an antimicrobial agent of the aminoglycoside family
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neomycin
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neomycin with __ exerts a highly complementary effect for lowering cholesterol levels?
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niacin
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Name two indications for neomycin?
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familial hypercholesterolemia
familial combined hyperlipidemia |
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what two combinations are effective in lowering LDL-C
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statin and resin (cholestyramine and colestipol)
or niacin and resin |
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what combination can be used to lower triglycerides in severe hypertriglyceridemia
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gemfibrozil and fish-oil capsules
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chylomicronemia
manifests as... use ... combo |
inc chylomicrons and inc VLDL
use niacin and fibrate |
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familial hypertriglyceridemia
manifests as ... use ... combo |
inc chylomicrons and inc VLDL
use niacin and fibrate |
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familial combined hyperlipoproteinemia manifests as...
use ... combo |
inc VLDL and inc LDL
use niacin and resin or statin |
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familial hypercholeterolemia heterozygous manifests ...
use ... combo |
inc LDL
use niacin, statin and or resin |
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familial hypercholesterolemia homozygous manifests as ...
use ... combo |
inc LDL
niacin and atorvastatin |
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Lp(a) hyperlipoproteinemia manifests as ...
use ... combo |
inc Lp(a)
use niacin and neomycin |