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Hyperlipidemia Flashcards

1
Q

Macromolecule complexes that transport lipids of human plasma

A

Lipoproteins

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2
Q

Metabolic disorders that involve an increase in levels of any of the lipoprotein species

A

Hyperlipoproteinemias or Hyperlipidemias

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3
Q

Increased levels of triglycerides in plase

A

Hyperlipidemia

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4
Q

Marked hyperlipidemia causes life-threatening…

A

Acute pancreatitis

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5
Q

Spherical particles with hydrophobic core regions containing cholesteryl esters and triglycerides. Unesterified cholesterol, phospholipids, and apoproteins surround the core

A

Plasma lipoproteins

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6
Q

This lipoprotein contains very high molecular weight B-48 apoproteins (ApoB-48)

A

Chylomicrons

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7
Q

Where is ApoB-48 formed?

A

Intestines

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8
Q

Is VLDL a very low-density molecule, intermediate-density, or low-density?

A

Very low-density

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9
Q

Is IDL a low-density molecule, intermediate-density, or low-density?

A

Intermediate-density

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10
Q

Is LDL a low-density molecule, intermediate-density, or low-density?

A

Low density

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11
Q

What lipoproteins contain very high-molecular weight B-100 apoproteins (ApoB-100)?

A

VLDL, IDL, LDL

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12
Q

Where is ApoB-100 synthesized?

A

Liver

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13
Q

Proved structural stability to the lipoproteins

A

apoproteins

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14
Q

A number of apoproteins function as ________ in lipoprotein-receptor interactions or as ________ in enzymatic processes that regulate lipoprotein metabolism

A

ligands; cofactors

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15
Q

Formed in the intestine and carry triglyerides of dietary origin, cholesterol, and cholesteryl esters

A

Chylomicrons

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16
Q

The triglycerides are removed from the chylomicrons in _________ tissues

A

extrahepatic

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17
Q

Triglycerides in chylomicrons are hydrolyzed by what enzyme to free fatty acids?

A

lipoprotein lipase

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18
Q

Where is VLDL secreted from?

A

Liver

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19
Q

VLDL exports ________ to peripheral tissues

A

triglycerides

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20
Q

Where is IDL formed from?

A

VLDL

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21
Q

Some IDL are endocytosed directly by the ______; the rest are converted to ______ by further removal of triglycerides

A

liver; LDL

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22
Q

What mediates the removal of triglycerides in IDL?

A

LPL and hepatic lipase

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23
Q

How is LDL formed?

A

from VLDL (via IDL)

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24
Q

Which lipoprotein delivers cholesterol to hepatocytes and other cells?

A

LDL

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25
Catabolism of LDL in hepatocytes and other cells involves ________________
receptor-mediated endocytosis
26
__________ from the LDL core are hydrolyzed, yielding free cholesterol which is used for the synthesis of cell membranes
Cholesteryl esters
27
High-density lipoproteins that exert antiatherogenic effects
HDL
28
They retrieve cholesterol from the artery wall and peripheral tissues that inhibit the oxidation of atherogenic liproteins
HDL
29
Where does much of the lipid in HDL come from during lipolysis?
Chylomicrons and VLDL
30
HDL can deliver cholesteryl esters directly to the liver via the ____________ which does not endocytose the lipoproteins
Scavenger Receptor (SR-BI)
31
Where is cholesterol synthesized?
Hepatocytes
32
How is cholesterol synthesized in the hepatocytes?
via the HMG-CoA reductase pathway
33
Cholesterol is exported from the hepatocytes to the general circulation via ________
VLDL
34
Hepatocytes are capable of eliminating cholesterol by secretion of cholesterol in the bile and by converting cholesterol to _______
bile acids
35
Which class of drugs is the first choice and are the most effective in reducing LDL levels?
HMG-CoA reductase inhibitors (Statins)
36
HMG-CoA reductase enzyme converts HMG-CoA to ______ (cholesterol biosynthesis)
mevalonate
37
The statins are _______ inhibitors of HMG-CoA reductase enzyme and ______ of HMG-CoA intermediates
competitive, structural analogs
38
Statins inhibit the ________ synthesis of cholesterol, leading to a decrease in cholesterol levels
de novo
39
Niacin is also known as ______
Vitamin B3
40
Modifies all plasma lipoproteins and lipids favorably
Niacin
41
Niacin is promoted for the treatment of _______
hypertriglyceridemia
42
Niacin inhibits ______ secretion from the hepatocytes, which leads to a decrease in the production of LDL
VLDL
43
Niacin inhibits the intracellular lipase of adipose tissue via receptor-mediated signaling, which leads to (increase or decrease?) in the flux of free fatty acids to the liver
decrease
44
The inhibition of intracellualr lipase reduces ______ production in the liver
VLDL
45
Niacin ________ the clearance of VLDL via the LPL pathway, which leads to a decrease in triglyceride levels
induces
46
Does Niacin increase or decrease the catabolic rate for HDL?
decrease
47
Name the fibric acid derivatives
Gemfibrozil Fenofibrate Fenofibric Acid
48
Do fibric acid derivatives decrease or increase the levels of VLDL in plasma?
decrease
49
Fibric acid derivatives lower ____________ by 30-50% and may increase _______ cholesterol
triglycerides; HDL
50
When fibric acid derivatives decrease elevated triglycerides, LDL cholesterol may increase or decrease?
increase
51
Which fibric acid derivative is the only fibrate with demonstrated beneficial effects on CV outcomes
Gemfibrozil
52
Fibrates are useful in hypertriglyceridemias in which ________ predominate
VLDL
53
Which drugs bind to PPAR-alpha and induce lipolysis of VLDL triglycerides via LPL, which results in a decrease in VLDL levels?
Fibric Acid Derivatives
54
What is cholesterol metabolized in the liver to?
Bile acids
55
Where are bile acids excreted to via the bile?
intestine
56
Where are bile acids efficiently reabsorbed?
jejunum and ileum
57
Are bile acid sequestrants soluble or insoluble in water?
insoluble
58
Name the bile acid sequestrants
Colestipol Cholestyramine Colsevelam
59
Name the selective inhibitor of intestinal absorption of both dietary and biliary cholesterol and phytosterols
Ezetimibe
60
What is the target for Ezetimibe?
a transport protein (NPC1L1) for cholesterol and phytosterols (plant sterols)
61
What is Ezetimibe's primary clinical effect?
reduction of LDL levels in plasma
62
Which class of drugs is Ezetimibe synergistic with in reducing LDL-cholesterol levels?
statins
63
Name the Omega-3 polyunsaturated fatty acids (PUFA) (fish oil)
Lovaza | Vascepa
64
What are the two most important omega-3 PUFAs?
``` Eicosapentaenoic Acid (EPA) Docoshaexanoic Acid (DHA) ```
65
Which omega-3 PUFA contains the ethyl esters of both EPA and DHA?
Lovaza
66
Which omega-3 PUFA contains only EPA as the ethyl ester?
Vascepa
67
What is the MOA of omega-3 PUFAs?
They decrease triglyceride levels by reducing hepatic triglyceride production and increasing triglyceride clearance
68
Name the antisense oligonucleotide
Mipomersen
69
Mipomersen is an antisense oligonucleotide inhibitor of?
ApoB-100 synthesis
70
What is the principal apoprotein in LDL and VLDL lipoproteins?
ApoB-100
71
__________ is a synthetic strand of nucleic acid, binds to mRNA that encodes ApoB resulting in degradation or disruption of the mRNA. This leads to a decrease in the synthesis of ApoB and a decrease in the synthesis of VLDL and LDL
Mipomersen
72
Decreased synthesis of VLDL and LDL leads to a (increase or decrease?) in plasma levels of LDL-cholesterol
decrease
73
Name the Microsomal Triglyceride Transfer Protein (MTP) Inhibitor
Lomitapide
74
What drug is both a substrate and an inhibitor of CYP3A4? It is also an inhibitor of the active-efflux transporter P-glycoprotein (P-gp)
Lomitapide
75
Lomitapide is contraindicated for use with other inhibitors of _________
CYP3A4
76
Where is microsomal triglyceride transfer protein (MTP) located?
in the lumen of the ER of hepatocytes and enterocytes
77
What is the function of MTP?
the assembly/formation of ApoB-containing lipoproteins in the liver and intestine
78
What binds to and inhibits MTP?
Lomitapide
79
Since Lomitapide inhibits MTP and the synthesis of chylomicrons and VLDL, what is the result?
LDL will not be synthesized from VLDL, leading to a significant reduction in plasma levels of LDL-cholesterol.
80
What is transcriptionally regulated by the content of cholesterol on the cell?
Production of LDL receptors and HMG-CoA reductase enzyme
81
Increased plasma levels of LDL can result from?
Increased secretion of VLDL, increased levels of IDL, decreased LDL catabolism and decreased LDL receptors
82
Cholesterol is delivered to the liver by
LDL, HDL, remnants of VLDL and chylomicrons
83
Fibric acid derivatives are ____ for ____
ligands, PPAR-alpha
84
Which omega-3 PUFAs are poor substrates responsible for triglyceride synthesis and inhibit esterification of other fatty acids?
EPA and DHA

Drug Mech Final (7 decks)

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