Treatment of Hyperlipidemias

Question 1

Lipoproteins

Answer 1

high mw complexes of specific proteins and lipids; transport triglycerides and cholesterol in the blood

Question 2

lipids used for

Answer 2

energy production (triglycerides) and membrane synthesis (cholesterol)

Question 3

larger, less dense lipoproteins contain

Answer 3

more triglycerides

Question 4

chylomicrons

Answer 4

only lipoproteins that have apolipoprotein b48

Question 5

Exogenous pathway

Answer 5

chylomicrons synthesized in enterocytes transport dietary lipids from circulation
20% of body’s cholesterol from food

Question 6

Endogenous pw

Answer 6

VLDL synthesized in hepatocytes transports FA and cholesterol to peripheral tissues
80% of body’s choletserol
Affected by dietary fat intake

Question 7

LDL

Answer 7

longest half life
70% of total plasma cholesterol
elevated is a major RF for atherosclerosis
migrates into vascular intima and can form plaques

Question 8

HDL

Answer 8

draws free cholesterol from cholesterol rich cells and takes it back to liver “reverse cholesterol transport” and transformed into bile or vldl
-synthesized by liver
-

Question 9

Lp(a) lipoprotein

Answer 9

Formed from LDL and apo(a)

can be found in plaques

Question 10

Primary hypertriglyceridemia

Answer 10

High triglycerides (200-500 mg/dL)

Question 11

Familial hypertriglyceridemia

Answer 11

develops with age, weight gain, diabetes

Tx dietary, weight reduction, exercise

Question 12

Rare primary hypertriglyceridemia

Answer 12

Familial lipoprotein lipase def

ApoCII def

Question 13

Primary hypercholesterolemia

Answer 13

High cholestserol (250-500 mg/dl) w. normal triglycerides (150 mg/dL)

Question 14

Familial hypercholesterolemia

Answer 14

defects in LDL receptor
elevated cholesterol levels from birth- requires treatment
Responds well to statins and lipid lowering drugs

-homozygous is rare- levels of 1000 mg/dl possible- cardiovascular disease in childhood

Question 15

Familial defective apoB100

Answer 15

mutation leads to dec affinity to LDL receptor

responds well to statins and niacin

Question 16

Mixed hyperlipidemia

Answer 16

elevated total cholestero, ldl, triglycerides

hdl reduced

Question 17

familial combined hyperlipidemia

Answer 17

common
w/ obesity, hyperinsulinemia, glucose intolerance
statins, combined maybe with fibrates and niacin

Question 18

Dysbetalipoproteinemia

Answer 18

defects in apoE

inc cholymicrons and IDL-like particles; tx- decrease fat and cholesterol intake; niacin and fibrates

Question 19

LDL, cholesterol, hdl levels

Answer 19

LDL <100 optimal
Total <200 desirable
HDL >60 good

Question 20

4 groups of ppl that should be treated with statin

Answer 20

individuals with:

1) clinical atherosclerotic cardiovascular events
2) LDL-c >190 mg/dl
3) 40-74 years of age with diabetes with LDL-c 70-189 mg/dl
4) 40-75 years w/o atherosclerosis with LDL 70-189 and estimated ASCVD risk of 7.5% or higher

Question 21

HDL apolipoprotein

Answer 21

A, C, E

Question 22

HMG-CoA reductase inhibitors

Answer 22

• statins
• atorvastatin, fluvastatin, rosuvastatin, pravastatin (active drugs)
• lovastatin, simvastatin (prodrugs)
• inhibit HMG-CoA reductase to reduce hepatic formation of cholesterol and increase LDL receptors in hepatocytes to lower plasma LDL
• decrease plasma triglycerides and increase HDL
• all have high first pass hepatic extraction and most excreted in bile

Question 23

Niacin

Answer 23

nicotinic acid, vit b3

Question 24

fibric acid derivatives

Answer 24

gemfibrozil and fenofibrate

Question 25

bile acid binding resins

Answer 25

colestipol, cholestyramine, colesevelam

Question 26

intestinal sterol absorption inhibitor

Answer 26

ezetimibe

Question 27

pleiotropic statin effects

Answer 27

-reversal of endothelial dysfunction- improved response to NO -dec inflammation dec coagulation improved plaque stability

Question 28

therapeutic uses for statins

Answer 28

elevated LDL levels reduce mortality from MI and CVD pts at high risk best given at night when most cholesterol synthesis occurs contra in pregnancy

Question 29

statin toxicity

Answer 29

hepatic toxicity | -indicated by elevations in serum aminotransaminase

Question 30

statin metabolized by CYP3A4

Answer 30

atorvastatin, lovastatin, simvastatin

Question 31

statin metabolized by CYP2c9

Answer 31

fluvastatin and rosuvastatin

Question 32

what statin is not metabolized by p450

Answer 32

pravastatin

Question 33

statin toxicity other

Answer 33

skeletal muscle- increased creatinine kinase activity -low dose, lower AE - when combining with fibrates (gemfibrozil) will increase rhabdomyolysis - measure serum aminotransferase and creatinine kinase - no simvastatin and amiodarone together because of rhabdomyolysis

Question 34

Niacin

Answer 34

water soluble B3 vitamin converted to the amide -large doses improve every lipid parameter -reduce ffa flux to liver -dec hepatic synthesis of trglycerides and vldl -lower plasma ldl -most effective for elevating hdl will cause some cutaneous flushing (inc prostaglandins)

Question 35

Fibric acid derivatives

Answer 35

Gemfibrozil and fenofibrate ligands for PPAR-alpha in hepatocytes (peroxisome proliferator activated receptor alpha) -activation decreases plasma triglycerides, VLDL and LDL and increases plasma HDL -used for hypertriglyceridemia and dysbetalipoproteinemia

Question 36

Fibric acid derivatives toxicities

Answer 36

``` skin rashes gi symptoms dec in wbc or hematocrit rarely rhabdomyolysis avoid in pts with hepatic or renal dysfunction modest risk of cholesterol gallstones myopathy inc in combo with statins ```

Question 37

omega 3

Answer 37

activate pparalpha | reduce triglycerides

Question 38

bile acid binding resins

Answer 38

colestipol, cholestyramine, colesevelam - bind bile acids and increase excretion - used in primary hypercholesterolemia, might result in inc of vldl, may be used for treating digoxin toxicity no systemic effects- no side effects may decrease absorption of vitamins adek impair absorption of certain drugs like digoxin, thiazides, tetracyclin, fluvastatin, thyroxne, aspirin

Question 39

ezetimibe

Answer 39

inhibits intestinal absorption of cholesterol and phytosterols -reduces ldl and minimal inc in hdl -tx of primary hypercholesterolemia low incidence of reversible hepatic impairment

Question 40

simcor

Answer 40

extended release niacin plus simvastatin

Question 41

vytorin

Answer 41

ezetimibe plus simvastatin