Treatment of Hyperlipidemias Flashcards
Lipoproteins
high mw complexes of specific proteins and lipids; transport triglycerides and cholesterol in the blood
lipids used for
energy production (triglycerides) and membrane synthesis (cholesterol)
larger, less dense lipoproteins contain
more triglycerides
chylomicrons
only lipoproteins that have apolipoprotein b48
Exogenous pathway
chylomicrons synthesized in enterocytes transport dietary lipids from circulation
20% of body’s cholesterol from food
Endogenous pw
VLDL synthesized in hepatocytes transports FA and cholesterol to peripheral tissues
80% of body’s choletserol
Affected by dietary fat intake
LDL
longest half life
70% of total plasma cholesterol
elevated is a major RF for atherosclerosis
migrates into vascular intima and can form plaques
HDL
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
-
Lp(a) lipoprotein
Formed from LDL and apo(a)
can be found in plaques
Primary hypertriglyceridemia
High triglycerides (200-500 mg/dL)
Familial hypertriglyceridemia
develops with age, weight gain, diabetes
Tx dietary, weight reduction, exercise
Rare primary hypertriglyceridemia
Familial lipoprotein lipase def
ApoCII def
Primary hypercholesterolemia
High cholestserol (250-500 mg/dl) w. normal triglycerides (150 mg/dL)
Familial hypercholesterolemia
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
Familial defective apoB100
mutation leads to dec affinity to LDL receptor
responds well to statins and niacin
Mixed hyperlipidemia
elevated total cholestero, ldl, triglycerides
hdl reduced
familial combined hyperlipidemia
common
w/ obesity, hyperinsulinemia, glucose intolerance
statins, combined maybe with fibrates and niacin
Dysbetalipoproteinemia
defects in apoE
inc cholymicrons and IDL-like particles; tx- decrease fat and cholesterol intake; niacin and fibrates
LDL, cholesterol, hdl levels
LDL <100 optimal
Total <200 desirable
HDL >60 good
4 groups of ppl that should be treated with statin
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
HDL apolipoprotein
A, C, E
HMG-CoA reductase inhibitors
- 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
Niacin
nicotinic acid, vit b3
fibric acid derivatives
gemfibrozil and fenofibrate
bile acid binding resins
colestipol, cholestyramine, colesevelam
intestinal sterol absorption inhibitor
ezetimibe
pleiotropic statin effects
-reversal of endothelial dysfunction- improved response to NO
-dec inflammation
dec coagulation
improved plaque stability
therapeutic uses for statins
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
statin toxicity
hepatic toxicity
-indicated by elevations in serum aminotransaminase
statin metabolized by CYP3A4
atorvastatin, lovastatin, simvastatin
statin metabolized by CYP2c9
fluvastatin and rosuvastatin
what statin is not metabolized by p450
pravastatin
statin toxicity other
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
Niacin
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)
Fibric acid derivatives
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
Fibric acid derivatives toxicities
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
omega 3
activate pparalpha
reduce triglycerides
bile acid binding resins
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
ezetimibe
inhibits intestinal absorption of cholesterol and phytosterols
-reduces ldl and minimal inc in hdl
-tx of primary hypercholesterolemia
low incidence of reversible hepatic impairment
simcor
extended release niacin plus simvastatin
vytorin
ezetimibe plus simvastatin
