Term
| Fxns of apolipoproteins (3) |
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Definition
Stabilize lipid particles
Act as recognition molecules for the binding of lipid particles to different receptors
Activate enzymes that metabolize lipid particles |
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Term
| Lipoproteins by size and density |
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Definition
Chylomicrons
Chylomicron remnants
VLDL
IDL
LDL
HDL |
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Term
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Definition
| Carry dietary lipids (cholesterol and TG) from GI tract to liver and other tissues |
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Term
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Definition
Carries cholesterol from non-hepatic tissue back to the liver
Scavenges free cholesterol from the plasma and cells of the intimal wall of arteries |
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Term
| TG are mostly ___ in origin while cholesterol is mostly ___ |
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Definition
Dietary
Synthesized in the liver (600 mg absorbed, 600 mg lost to feces) |
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Term
| How is the truck (lipoprotein) unloaded? |
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Definition
ApoB48 delivers the chylomicron to the tissue
Lipoprotein lipase on endothelial surface in striated muscle and fat
ApoCII activates LPL
LPL converts TGs (and only TGs) to FFAs, which can be oxidized immediately to make energy or can be re-esterified for storage in adipocytes
Most of the cholesterol remains on the truck, although some is "dragged" out by the LPL and will need to be cleaned up by someone else |
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Term
| What happens to an unloaded chylomicron? |
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Definition
Liver LDL-receptor related protein (LRP) binds the ApoE in the remnant
Remnant is removed from the bloodstream
Cholesterol is unloaded from the remnant and b/c part of the sterol pool |
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Term
|
Definition
LDL = Tc - (HDL + VLDL)
VLDL = TG/5 |
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Term
| Normal lipoprotein values |
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Definition
LDL: <100 mM/L for mod. high-risk, <70 for v. high-risk
HDL: >40, 50 in women
TG: <150 |
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Term
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Definition
Absolute value of LDL and absolute value of fasting TGs
HDL levels are inversely related |
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Term
| Broad strategies to improve the lipid profile = dec. CV risk (2) |
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Definition
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Term
| Specific ways to lower plasma LDL (4) |
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Definition
Dec. plasma TG
Dec. synthesis of ApoB100 to dec. hepatic synthesis of VLDL
Inc. expression of hepatic LDL-R
Inc. clearance of VLDL and IDL |
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Term
| Specific ways to lower plasma TG (2.3) |
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Definition
Dec. synthesis of ApoB100 = dec. hepatic synthesis of VLDL
Activate peroxisome proliferator-activated receptor a (PPARa):
a. Inc ox. of FA = dec. available substrate for TG synthesis
b. Inc. synthesis of LPL = inc. clearance of VLDL
c. Dec. expression of ApoCIII gene (this inhibits receptor-mediated, lipolytic clearance of VLDL) |
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Term
| Specific ways to inc. HDL |
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Definition
| Inc. synthesis of ApoAI and ApoAII |
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Term
| First line drugs for lipid profile management |
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Definition
| HMG CoA reductase inhibitors |
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Term
| HMG CoA reductase inhibitors end in... |
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Definition
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Term
| Statins that aren't metabolized by a CYP (2) |
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Definition
Pravastatin: excreted unchanged in urine
Rosuvastatin: 90% eliminated in feces, rest metabolized by CYP |
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Term
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Definition
Inhibit sterol synthesis
Dec. intracellular [sterol]
Inc. synthesis of HMG CoA reductase (compensates for inhibition to 75-80% of normal) and LDL-R
(not as effective in genetic absence of hepatic LDL-R)
Dec. synthesis of ApoB100 = dec. hepatic synthesis of VLDL
Causes inc. clearance of VLDL from plasma |
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Term
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Definition
VLDL: dec. 10-25%
LDL: dec. 25-45%
TGs: dec. 10-30%
HDL: inc. 8-10% |
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Term
| Atorvastatin produces a ___ in LDL |
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Definition
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Term
To dec. LDL 25-30% use ___ statins.
To dec. LDL 30-35% use ___ statins. |
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Definition
Any statin
Atorvastatin, rosuvastatin, simvastatin |
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Term
| What effect do statins have on MI? |
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Definition
| Dec. 2nd MI by 50% even though it has little effect on luminal stenosis |
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Term
| Statins: other cardioprotective effects |
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Definition
Inc. stability of cholesterol plaques
Reverse endothelial dysfxn, inc. ability to synthesize NO
Dec. oxidation of LDL
Dec. CRP levels |
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Term
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Definition
Hepatic damage
Fetal toxicity
Myopathy from dysfxn of mito respiration
Inc. w/ statin + gemfibrozil/niacin
Inc. w/ inhibition of CYP + atorvastatin/simvastatin
(Inhibitors: clarithromycin, fluconazole, metronidazole, verapamil, amiodarone)
Can lead to fatal rhabdomyolysis |
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Term
| Ezetimibe: pharmacokinetics |
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Definition
Rapidly absorbed and conjugated
Extensive enterohepatic recirculation = t1/2 of 22h
But most of p.o. dose is excreted in feces |
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Term
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Definition
| Inc. hepatic LDL-R expression via sterolstat |
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Term
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Definition
| Inc. hepatic LDL-R expression via the sterolstat |
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Term
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Definition
Blocks protein-mediated transporter that brings in dietary cholesterol from GI tract by 50% (no effect on fat-soluble vitamins, TGs, estradiol, progesterone)
Sterol pool depleted
Inc. synthesis of HMG CoA reductase (compensates for inhibition to 80-90% of normal) and LDL-R |
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Term
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Definition
VLDL: nc
LDL: dec. 15-20%
TGs: dec. 5-10%
HDL: inc. 2-4% |
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Term
| Ezetimibe + simvastatin produce ___ |
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Definition
An additive dec. in LDL, TG
So can lower the dose of simvastatin when given w/ ezetimibe = avoid statin S/E |
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Term
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Definition
Hepatic damage
Prego C
Doesn't augment statin myopathy
Doesn't affect CYPs |
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Term
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Definition
| Everyone at risk including DM |
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Term
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Definition
| Hyperlipidemia when you can't reach your target LDL using statins alone |
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Term
| Ion-exchange resins = bile acid sequestrants |
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Definition
Cholestyramine
Colesevelan
Colestipol |
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Term
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Definition
| Inc. hepatic LDL-R expression via the sterolstat |
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Term
| Drugs that inc. hepatic LDL-R expression |
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Definition
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Term
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Definition
Swap Cl for negatively-charged bile acids = bile acids lost to feces
Sterol pool depleted
Inc. synthesis of HMG CoA reductase (compensates for inhibition) and LDL-R |
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Term
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Definition
VLDL: nc
LDL: dose-related dec. 10-35%
TGs: nc
HDL: inc. <5% |
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Term
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Definition
Constipation, bloating, pain
May conjugate w/ other drugs and prevent their absorption but not colesevelan (fluvastatin, furosemide, HCTZ, pravastatin, propanolol, tetracyclines, thyroxine)
Avoided by taking the other drug 1 hr before or 4 hrs after taking the resin
Colesevelan: Prego B
Cholestyramine: Prego C |
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Term
| Niacin = vitB3: MOA summary (5) |
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Definition
Dec. hepatic synthesis of TGs
Dec. VLDL
Dec. IDL, shift of LDL towards larger, less easily oxidized LDL
Dec. LDL, Tc (b/c dec. VLDL, IDL)
Inc. HDL b/c dec. catabolism of ApoA1 |
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Term
| Niacin: MOA effect on TGs |
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Definition
Inhibit lipolysis
Dec. FFA
Dec. precursors for TGs |
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Term
|
Definition
Dec. hepatic synthesis of TG
Dec. hepatic synthesis and esterification of FA = inc. degradation of ApoB100
Inc. clearance of VLDL via LPL |
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Term
|
Definition
Response depends on initial value
<30 then response is attenuated
>30 then response is much bigger |
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Term
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Definition
VLDL: dec.
LDL: dec. 20-25%
TGs: dec. 35-50%
HDL: inc. 15-30% |
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Term
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Definition
Adjunct tx b/c of S/E
Pt w/ elevated TG and low HDL = dyslipidemias = NIDDM
Pt w/ hyperlipidemias |
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Term
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Definition
Prego C
Flushing and pruritis, dec. w/ time or aspirin
n/v/d, dyspepsia
Dry skin
Gout symptoms
Hepatic damage |
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Term
| Fibrates and general purpose |
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Definition
Fenofibrate
Gemfibrozil
Tx hyperTG! |
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Term
|
Definition
Bind to PPARa in liver, brown fat, striated muscle, kidney
Inc. peroxisomes = inc. oxidation of FA
Inc. synthesis of LPL
Dec. expression of ApoCII gene (inhibits receptor-mediated and lipolytic clearance of VLDL) = inc. clearance of VLDL = dec. TG
Stim. ApoAI and ApoAII genes = inc. HDL
Inc. release of SREBP = inc. expression of hepatic LDL-R = dec. LDL |
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Term
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Definition
VLDL: dec. 50%
LDL: dec. 15-20%
TGs: dec. 50%
HDL: inc. 10-20% |
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Term
| Fibrates cause a greater dec. in ___ while statins cause a greater dec. in ___ |
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Definition
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Term
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Definition
Single agent to dec. VLDL, LDL, and TGs and inc. HDL
Dec. VLDL and TGs and inc. HDL in pt on statins (NIDDM)
Pt w/ hyperTG + at risk for pancreatitis |
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Term
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Definition
Prego C
GI issues
Myopathy, and augments myopathy when in combo w/ statin
Gallstones
Don't use in pt w/ renal or hepatic disease |
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Term
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Definition
Activate PPARa = enhance FA oxidation in liver and skeletal muscle = dec. substrate for VLDL synthesis
Inc. degradation of ApoB100 = dec. secretion of VLDL
Activate LPL = inc. clearance of VLDL
Inc. hepatic glycogen synthesis |
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Term
| Omega 3 FA: lipid profile |
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Definition
LDL: dec. 5-10%
TGs: 25-30% |
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Term
| VLDL needs ___ to be secreted from the liver |
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Definition
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Term
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Definition
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Term
| Inc. intake of carbs causes... |
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Definition
Inc. formation of VLDL
Inc. secretion of VLDL
At adipocytes and muscle ApoCII activates LPL
LPL unloads TG and leaves behind cholesterol trash
Now called IDL |
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Term
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Definition
50% bind to hepatic LDL-R w/ ApoB100 and LRP w/ ApoE = removed from the blood
50% lose ApoE and are converted to LDL
100% of LDL comes from VLDLs |
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Term
| Why is HDL "good" cholesterol? |
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Definition
LPL-induced ApoCII, ApoCIII, and ApoE make unesterified cholesterol and other junk when they're unloading the chylomicrons and VLDLs
HDL ApoAI and ApoAII bind unesterified cholesterol and free cholesterol
Unesterified cholesterol esterified by LCAT = now non-polar, moves to center of HDL, and ApoAs are free to bind more stuff
HDL goes back to the liver or transfer its contents to VLDL and IDL |
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Term
| LDL is important in atherogenesis b/c... |
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Definition
| It's the major atherogenic lipoprotein, esp. if small (inverse correlation w/ TG levels) and/or when oxidized |
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Term
| Plasma [LDL] is determined by... |
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Definition
Dietary intake of cholesterol
Hepatic synthesis of VLDL
# of LDL-R on cells' surface (hepatic ones remove 75% of plasma LDL) |
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Term
| How are LDL-R and HMG CoA reductase genetically related to each other? |
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Definition
| SREBP binds to SRE and activates the gene promoter for LDL-R and HMG CoA reductase |
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