Antilipidemics (4) Flashcards
t/f thyroid hormones can have hypocholesterimic effects
true
what does dextrothyroxine require?
99% + pure optical isomer
dextrothyroxine overall effect
increase LDL receptors (enhance removal of LDL)
Dextrothyroxine stimulates the ______ of cholesterol in liver through increase of _______
oxidative catabolism
7a-cholesterol-hydroxylase
Adverse effects of dextrothyroxine
- increase frequency and severity of anginal attacks
- cause cardiac arrhythmias
- potentiates action of anticoagulants
Diabetics and dextrothyroxine
requires increased dose of insulin or hypoglycemic agents
What is a vitamin used as hypocholesteremic?
niacin
Niacin is effective for all types of hyperlipidemica except _____ at doses given as vitamin supplement
type I
niacin overall effect
- decrease VLDL synthesis (decrease IDL, LDL)
- inhibit lipolysis
What is the drug of choice for all type II hyperlipoproteinemias?
Niacin
Why is niacin have limited use?
vasodilation side effects
What is an extended release preparation of niacin?
Nispan
Probucol overall effect
decrease level of cholesterol by increasing rate of LDL catabolism
- may also inhibit cholesterol synthesis and delay cholesterol absorption
How does probucol decrease levels of cholesterol?
increasing rate of LDL catabolism
What is probucol believed to act on?
ABCA1
Why was probucol withdrawn from market?
cause QTc prolongation
Cholestyramine is a ______ that binds _____ in GI tract and prevents reabsorption
bile acid sequestrant
bile
Cholestyramine is a ____ resion with what type of group?
strong ion exchange resin
quaternary ammonium group
With cholestyramine, due to loss of bile acids, more ____ is converted to bild acids in liver to normalize levels
plasma cholesterol
cholestyramine overall effect
decrease plasma cholesterol levels
What does ACAT do?
catalyze cholesterol esterification and cholesterol absorption
maintain cholesterol homeostasis in blood
What is a new attractive target for hyperlipidemia?
ACAT inhibitors
ACAT1 regulates cholesterol homeostasis where?
brain
macrophages
adrenal glands
ACAT2 ____ cholesterol where?
esterfies
intestine and liver
What regulates cholesterol homeostasis in brain, macrophages and adrenal glands?
ACAT1
What esterfies cholesterol in small intestine and liver?
ACAT2
what is CIMT?
carotid intima media thickness
What does CETP do?
facilitates transport of cholesteryl esters and TGs between lipoproteins
What are CETP designed to do?
raise HDL (thought to be protective)
What can reverse transport of cholesterol out of macrophages?
CETP: so cholesterol can be metabolized
How does CETP work?
collects TGs from VLDL or LDL and exchange for cholesteryl esters from HDL
What CETP inhibitor does not have cardiovascular problems?
dalcetrapib
What CETP inhibitor is on the market?
NONE!
CETP inhibitors may produce a form of ____ that does not enhance reverse cholesterol transport
HDL
What is an adipose tissue derived adipokine?
resistein
resistin AKA
- ADSF or XCP1
resistin is a small, _____ protein secreted from ____
cysteine rich
macrophages and adipose tissue
resistin overall effect
increase LDL in human liver cells
degrae LDL receptors in liver
What is thought to be an important link between obesity and insulin resistance and diabetes?
resistin
serum levels of ____ are increased in human obesity and + correlated with ____
resistin
atherosclerotic CVD
At physiological levels observed in human obesity, resistin reduces human hepatocyte expression of ____
LDLRs
Statins are ineffective in 40% of patients due to ____ secretion in adipose tissue
resistin
____ may be new therapeutic target because statins may be ineffective in some
resistin
What is a key regulator of LDL-C metabolism?
PCSK9
PCSK9 has been shown to be stimulated by ____ and leads to what?
resistin
downregulation of LDLR
Resistin and PCSK9 have notable structural similarity where?
cysteine rich C terminal domain
Atherosclerosis is buildup of what lipoproteins?
LDL-C
PCSK9 inhibitors in transgenic mice lower ____
LDL
ODYSSEY long term study
65 weeks
alirocumab reduced risk of major events compared to those with placebo and max tolerated statin
ODYSSEY results
decrease LDL 61%
79% achieved target LDL <70 after treatment with alirocumab
Why were CETP inhibitor trials stopped?
lack of clinically meaningful efficacy
What are CETP inhibitors thought to do?
Increase HDL
What do PCSK9 inhibitors supposed to do?
decrease LDL
