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Cardiovascular > Pharmacology- Cholesterol > Flashcards

Pharmacology- Cholesterol Flashcards

1
Q

are lipids soluble in water

A

insoluble or sparing soluble in water

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2
Q

what are lipids essential for

A

membrane biogenesis and membrane integrity, energy sources, precursors for hormones and signalling molecules

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3
Q

what are two examples of non polar lipids

A

cholesterol esters and triglycerides

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4
Q

how are non polar lipids transported within the blood

A

within lipoproteins (e.g. HDL and LDL (high/low density)

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5
Q

what ratio of HDL and LDL is cardiovascular disease associated with (atherosclerosis)

A

elevated LDL and decreased HDL

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6
Q

what are the causes of a high LDL to HDL ratio

A

diet and lifestyle (western), genetic factors

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7
Q

what does the synthesis of all steroid hormones start with

A

cholesterol

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8
Q

describe the structure of lipoproteins

A

7-1000 nM in diameter, hydrophobic core and hydrophilic core

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9
Q

what does the hydrophobic core of lipoproteins contain

A

esterified cholesterol and triglycerides

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10
Q

what does the hydrophilic coat of lipoproteins contain

A

monolayer of amphipathic cholesterol, phospholipids and one/more apoproteins

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11
Q

what are the 4 major lipoproteins

A

HDL, LDL, VLDL (very low density), chylomicrons

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12
Q

what apoproteins do HDL particles contain

A

apoA1 and apoA2

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13
Q

what apoproteins do LDL particles contain

A

apoB-100

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14
Q

what apoproteins do VLDL particles contain

A

apoB-100

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15
Q

what apoproteins do chylomicrons particles contain

A

apoB-48

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16
Q

where do ApoB-containing lipoproteins deliver triglycerides to (2)

A

1- muscle for ATP biogenesis

2- adipocytes (fat cells) for storage

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17
Q

describe the exogenous pathway

A

Chylomicrons are formed in intestinal cells and transport dietary triglycerides

involves the absorption, distribution and delivery of lipids from diet to the periphery tissues

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18
Q

describe the endogenous pathway

A

VLDL particles are formed in liver cells and transport triglycerides synthesised in the liver

involves lipid synthesis by liver and delivery to peripheral tissue via VLD lipoproteins

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19
Q

describe the life cycle of apoB-containing liposomes

A

1- assembly; apoB100 (liver) and apoB48 (intestine)

2- intravascular metabolism; (ivloves hydrolyses of triglyceride core)

3- receptor mediated clearance

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20
Q

(assembly of chylomicrons)

what breaks down dietary fat first and where

A

lipases in the intestine (formed in the pancreas)

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21
Q

(assembly of chylomicrons)

what is dietary fat broken down into to enter the cells lining gut lumen (via diffusion)

A

monoglyceride and free fatty acid (long chain)

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22
Q

(assembly of chylomicrons)

what happens when the monoglyceride and free fatty acid chain are within the cell

A

triglyceride synthesis

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23
Q

(assembly of chylomicrons)

how is cholesterol transported into the cell

A

via Niemann-Pick C1-like 1 protein

NPC1L1

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24
Q

(assembly of chylomicrons)

what happens to cholesterol once it is inside the cell

A

esterification to make cholesteryl ester

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25
what is an enterocyte
cell of the intestine lining
26
(assembly of chylomicrons) | what does cholesteryl ester eventually form
apoB48
27
(assembly of chylomicrons) | what is the apoB48 produced in enterocytes added to
triglyceride droplets within cell
28
what is lipidation
the addition of hydrophobic molecules to a protein or chemical compound
29
(assembly of chylomicrons) | how what are the final stages of chylomicron formation
lipidation (assisted with MTP), and addition of cholesteryl ester and apoA1
30
(assembly of chylomicrons) | how does the chylomicron exit the cell and where does it go
exits via exocytosis and enters the lymphatics where it is carried in lymph to systemic circulation (subclavian vein) via the thoracic duct
31
where are VLDL particles assembeled
in liner hepatocytes
32
what are VLDL particles synthesised from
from free fatty acids from adipose tissue and de novo synthesis
33
what is the role of MTP in the assembly of VLDL particles
MTP lipidates apoB100 forming nascent VLDL that coalesces with triglyceride droplets
34
how are chylomicrons and VLDL particles activated (to deliver adipose and muscle tissue
the transfer of apoCII from HDL particles into the shell of VLDL and chylomicron particles
35
what is the role of HDL
mops up excess cholesterol in the blood and carry it to the liver where it is secreted in bile
36
what does the transfer of apoCII facilitate
facilitates binding of chylomicrons and VLDL particles to LPL
37
what is LPL
Lipoprotein lipase (LPL) – lipolytic enzyme associated with the endothelium of capillaries in adipose and muscle tissue
38
how does LPL act on VLDL and LPL
LPL hydrolyses core triglycerides to free fatty acids and glycerol which enter tissues
39
what are chylomicron and VLDL remnants
Particles depleted of triglycerides (but still containing cholesteryl esters)
40
what happens to apoCII after VLDL and chylomicrons dissociate from LPL
ApoCII is transferred to HDL particles in exchange for apoE. particles are now remnants
41
what is apoE
a high affinity ligand for receptor mediated clearance
42
where do the VLDL anf chylomicrons return to and what happens
return to liver and are further metabolised by hepatic lipase
43
what are all apoB48 containing remnants and 50% of all apo100 containing remnants cleared by
receptor-mediated endocytosis into hepatocytes
44
what happens to the remaining 50% of apoB100 containing lipoproteins not cleared by receptor mediated endocytosis
remnants loose further triglyceride through hepatic lipase, become smaller and enriched in cholesteryl ester and via intermediate density lipoproteins (IDL) become LDL particles lacking apoE and retaining solely apoB100
45
what is clearance of LDL dependant on
LDL receptor expression by the liver and other tissues (liver most important)
46
how does cellular uptake of LDL occur via
via receptor-mediated endocytosis
47
what is endocytosis
process of capturing a substance or particle from outside the cell by engulfing it with the cell membrane, and bringing it into the cell.
48
whats a lysosome
little enzyme package (organelle)
49
describe the release of cholesterol within the cell
released from cholesteryl ester (CE) at the lysosome via hydrolysis
50
what does released cholesterol cause
inhibition of HMG-CoA reductase which is the rate limiting enzyme in de novo cholesterol synthesis down regulation of LDL receptor expression storage of cholesterol as cholesterol ester
51
what do statins do
block the synthesis of cholesterol in the liver cell and thus increase surface expression of LDL receptors, therefore LDL cells more readily cleared form the plasma
52
what happens to LDL after it is taken into the endothelium of the artery from the blood
LDL is oxidised to atherogenic oxidised (OXLDL)
53
what initiates atherosclerosis
dysfunction and injury of the lining of blood vessels
54
describe the formation of fatty streaks in endothelium
monocytes migrate to across the endothelium into the intima where they become macrophages and uptake OXLDL and convert them to cholesterol-laden foam cells that form a fatty streak
55
what is a fatty streak a sign of
early event in atherosclerosis
56
describe the formation of an atheromatous plaque
release of inflammatory substances from various cell types causing division and proliferation (rapid increase in number) of smooth muscle cells in the intima and the deposition of collagen
57
describe the composition of an atheromatous plaque
a lipid core (product of dead foam cells) and a fibrous cap (smooth muscle cells and connective tissue)
58
why is HDL the good cholesterol
has a key role in removing excess cholesterol from cells by transporting it in plasma to the liver (reverse cholesterol transport)
59
where is HDL mainly formed
in the liver
60
in the plasma what mediates the transfer of cholesteryl esters indirectly returning cholesterol to the liver
cholesterol ester transfer protein (CETP)
61
what causes primary dyslipidaemia
combination of diet and genetic factors
62
what causes secondary dyslipidaemia
is a consequence of other diseases
63
what is dyslipidaemia
abnormal amount of lipids
64
what is the drugs of choice to reduce LDL
statins
65
give 2 example of statins
simvastatin and atorvastatin
66
what do statins act on and how
Act as competitive inhibitors of HMG-CoA reductase (limiting step in cholesterol synthesis in hepatocytes
67
how do statins reduce LDL levels
as decrease in hepatocyte cholesterol synthesis causes a compensatory increase in LDL receptor expression and enhanced clearance of LDL
68
what are other beneficial effects of statins
Decreased inflammation Reversal of endothelial dysfunction Decreased thrombosis Stabilization of atherosclerotic plaques
69
how are statins administered
orally at night
70
what do fibrates do
caused pronounced decrease in triglycerides and modest decreases in LDL and HDL
71
what are two examples of fibrates
bezafibrate and gemfibrozil
72
what are fibrates used to treat
very high triglyceride levels
73
how do fibrates act
as agonists of a nuclear receptor (PPARalpha) to enhance the transcription of several genes, including that encoding LPL
74
what adverse effect can statins and fibrates cause
myositis
75
give three examples of drugs that inhibit cholesterol absorption
colestyramine, colestipol, colsevelam
76
describe how bile acid binding resins work to inhibit cholesterol absorption
) cause the excretion of bile salts resulting in more cholesterol to be converted to bile salts by interrupting enterohepatic recycling
77
what do binding resins cause
decreased absorption of triglycerides increased LDL receptor function
78
what is ezetimibe
acts to inhibit NPC1L1 transport protein in enterocytes of the duodenum, reducing the absorption of cholesterol
79
what types of cholesterol does ezetimibe affect
decreases LDL but doesn't really affect HDL
80
describe the administration of ezetimibe
used in combo with statins when statins not enough. Not in breastfeeding females

Cardiovascular (34 decks)

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