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PMCOL 344 > Other lipid drugs > Flashcards

Other lipid drugs Flashcards

1
Q

what is an example of a fibrate

A

gemfibrozil

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2
Q

what is the mechanism of action of gemfibrozil

A

activates PPAR-α

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3
Q

where is PPAR-α expressed

A

liver, brown fat, kidney, heart, skeletal muscle

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4
Q

what is the effect of activating PPAR-α

A

alter genes that control lipid metabolism

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5
Q

what is a main important thing that PPAR-α activation does

A

increases fatty acid oxidation via increases LPL expression

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6
Q

what happens when you increase LPL expression

A

you enhance removal of TGs from CMs and VLDL

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7
Q

what happens to VLDL production with gemfibrozil

A

decreased

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8
Q

what happens to LDL production with gemfibrozil

A

decreased

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9
Q

what happens to apoA1 production with gemfibrozil

A

increased expression (HDL)

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10
Q

what happens to LDL receptor expression production with gemfibrozil

A

increased in hepatic tissue

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11
Q

how much does gemfibrozil reduce TGs and VLDL

A

by 25-50%

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12
Q

how much does gemfibrozil increase HDL

A

by 10-35%

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13
Q

what does gemfibrozil do to Bile

A

increase excretion

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14
Q

what does gemfibrozil do to inflammation

A

reduce

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15
Q

what does gemfibrozil do to endothelial function

A

improve

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16
Q

what does gemfibrozil do to glucose tolerance

A

improve

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17
Q

can gemfibrozil improve survival rates

A

maybe no

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18
Q

can gemfibrozil cause myositis and rhabdomyolysis

A

yes

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19
Q

what is a bad side effect of gemfibrozil

A

myositis and rhabdomyolysis

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20
Q

which patients do we give gemfibrozil to

A

patients with elevated LDL or VLDL or low HDL

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21
Q

what does gemfibrozil do to VLDL secretion

A

decrease

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22
Q

what does gemfibrozil do to LDL uptake

A

increase

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23
Q

what does gemfibrozil do to lipoprotein lipase

A

enhance

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24
Q

what are the 3 main things gemfibrozil does

A
  • decrease VLDL secretion
  • increase LDL uptake
  • enhance lipoprotein lipase
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25
where do resins act
GI tract
26
what was the first clinical method to lower cholesterol
resins
27
what is another name for resins
bile acid sequestrants
28
what is another name for bile acid sequestrants
resins
29
name an example bile acid sequestrants
colesevelam
30
how do resins work/ mechanism
they are +vely charged so they bind -vely charged bile acids to prevent reabsorption, leading to compensatory increase in bile synthesis from cholesterol
31
do resins work like cation or anion exchange
anion
32
what is a main important thing that resins lead to
increased hepatic expression of LDL receptors (wants more cholesterol to turn into bile acids)
33
what do resins do to cholesterol metabolism
increase its conversion into bile acids
34
what do resins do to plasma LDL + why
lower Liver is looking for more cholesterol to turn into bile acids, so more LDL is taken into liver and is removed from bloodstream
35
what do resins do to LDL receptors
increases hepatic expression of them
36
what is one main bad thing that resins cause
increases hepatic cholesterol and TG synthesis
37
how to prevent resin induced increases hepatic cholesterol and TG synthesis
use statins
38
what are some annoying side effects with resins
they cause bloating, need up to 32g a day
39
what can high doses of resins alone do to plasma cholesterol
lower by 25%
40
why do we do low doses of resins + statins for plasma cholesterol
because statins offset increased hepatic cholesterol synthesis
41
what is the mechanism of action of nicotinic acid / what does it do
limit the availability of free fatty acids to reduce hepatic TG synthesis via orphan receptor HM74A
42
what does nicotinic acid do in adipose tissue
inhibits lipolysis of TGs by hormone sensitive lipase
43
what happens once nicotinic acid inhibits lipolysis of TGs in adipose tissue
there will be less transport of free fatty acids to liver and so decreases hepatic TG synthesis -decreased plasma VLDL
44
what does nicotinic acid do in liver tissue
reduces TG synthesis by inhibiting synthesis and esterification of fatty acids - decrease plasma VLDL
45
what are 3 ways nicotinic acid decreases VLDL
- inhibit lipolysis of TGs in adipose tissue - reduce TG synthesis in liver - increase LPL activity
46
what does increases LPL activity cause
promotes clearance of CM and VLDL TGs - decreased plasma VLDL
47
what is the main fats that VLDL transport
TGs
48
what does nicotinic acid do to apoA-1 + what does this cause
decreases hepatic clearance of apoA-1, sp this increases HDL
49
what does nicotinic acid do to ABCA1 + what does this cause
increases its expression, so more transfer of free cholesterol from cells to HDL
50
which receptor does nicotinic acid work through
maybe the orphan receptor HM74A
51
how does nicotinic acid reduce liver TG synthesis
by inhibiting synthesis and esterification of fatty acid
52
what does decreased VLDL lead to
reduced plasma LDL
53
what can nicotinic acid do to HDL
increase by 30-40%
54
what can nicotinic acid do to VLDL
decrease by 35-45% (also also plasma TGs)
55
what can nicotinic acid do to LDL
decrease by 20-30%
56
what is special about nicotinic acid
it is the only agent to significantly reduce Lp(a)
57
what is the only agent that can significantly reduce Lp(a)
nicotinic acid
58
which patients do we use nicotinic acid for
with high TGs and high LDL and low HDL
59
does nicotinic acid improve outcome
maybe no :( even though it helps lipids
60
what is ezetimibe
cholesterol absorption inhibitors
61
what mediates intestinal cholesterol absorption
NPC1L1 in epithelium
62
what is the mechanism of ezetimibe
selectively block absorption of cholesterol in duodenum by NPC1L1
63
does ezetimibe affect absorption of fat soluble vitamins
no
64
does ezetimibe affect absorption of cholesterol
yes
65
does ezetimibe affect absorption of TGs
no
66
does ezetimibe affect absorption of bile acids
no
67
why do we call ezetimibe potent
it binds to protein receptor rather than directly interacting with cholesterol
68
how much can ezetimibe reduce cholesterol asborption
by 55%
69
what kind of people should take ezetimibe and who shouldnt
do it if you have high dietary cholesterol (it wont do much if you have low cholesterol diet or if excessive production of liver disease)
70
what class is ezetimibe
inhibition of cholesterol absorption
71
what does ezetimibe do to CM
decreases them so decreases CM remnant-mediated delivery of cholesterol to the liver
72
what does ezetimibe do to plasma LDL and how
reduction in hepatic cholesterol increases LDL receptors so more uptake and less plasma (20%)
73
what can be a bad thing about ezetimibe
increases hepatic cholesterol synthesis
74
how do you counteract ezetimibe induced hepatic cholesterol synthesis
give a statin too
75
how clinically useful may ezetimibe be
maybe not that much
76
which drug has the biggest decrease in LDL
statins
77
which drug has the smallest decrease in LDL
fibrates and absorption inhibitors
78
rate the drugs in order of largest to smallest decrease in LDL
statins>resins>nicotinic acid>fibrates = absorption inhibitors
79
which drug has the biggest increase in HDL
nicotinic acid
80
which drug has the smallest increase in HDL
resins and absorption inhibitors
81
rate the drugs in order of largest to smallest increase in HDL
nicotinic acid>fibrates>statins>resins>absorption inhibitors
82
which drug has the biggest decrease in TGs
nicotinic acid
83
which drug increases TGs
resins
84
rate the drugs in order of largest to smallest decrease in TGs
nicotinic acid>fibrates>statins> absorption inhibitors>> resins(they increase!)

PMCOL 344 (27 decks)

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