Dyslipidemia Flashcards
Test 4
Define dyslipidemia
High cholesterol
Pathologic level of lipids in the bloodstream
What is the leading cause of death in the US?
Atherosclerosis
What is Atherosclerosis?
Lipid deposits in coronary arteries which can lead to an ischemic event (MI, stroke)
Describe the process of atherogenesis
- Low-density lipoprotein (LDL) - cholesterol-carrier molecule produced in liver and distributes cholesterol throughout the body
- Excessive LDL leads to increased cholesterol molecules deposited under endothelial lining of the intima of arteries (connective tissue) → WBCs migrate into area and converge into Macrophages
- Macrophages are pro-inflammatory and are able to recognize cholesterol via CD36 and SR-A receptors → Macrophages swallow up the cholesterol → ROS, SO, HP, metalloproteinase and other pro-inflammatory markers are released → LDL is oxidized and becomes antigenic
- Oxidized LDL can reenter blood stream → antibodies produced against it enter the area and form immune complexes → elevates immune response even more→ calcification of destroyed cells
- Macrophages can’t break down cholesterol b/c unable to break steroid ring ; it can be turned into bile acids so the cholesterol builds up inside macrophages more and more and are called foam cell (spongy large appearance) → cholesterol begins to crystallize in foam cell → foam cell ruptures → calcified necrotic plaque formed in vessel
What are all the types of lipids?
Free fatty acids
phospholipids
cholesterol
triglycerides
Glycolipids
prostaglandins
Increasing triglycerides _______ risk for metabolic syndrome
increases
Describe Triglyceride
glycerol ester combined with free fatty acids
form adipose tissue/fat
majority neutral fats
used as energy during fasting or between meals
What is the main storage form of fat in humans?
triglyerides
A cholesterol is a _____ molecule
sterol
What is cholesterol a precursor to?
steroid hormones
cell membranes
vitamin D
bile salts
Describe a choleterol structure
3-6 carbon rings with a -OH tail attached to a 5 carbon ring
adding side chains through metabolism & enzymes changes the molecule
How do we get cholesterol?
- diet
- de novo synthesis: liver makes cholesterol
T/F: diet alone can fix high cholesterol
F
only 20% of cholesterol comes from diet
need medications
What is the precursor & enzyme for cholesterol?
HMG-CoA
HMG-CoA reductase
What does HMG-CoA convert to? What enzyme is needed for this?
Mevalonate
HMG-CoA reducatase
Where is cholesterol made?
Liver
Describe lipoproteins
Circulate in the bloodstream & carry cholesterol/lipids in a shell bc they are not water soluble
Consist of “apolipoprotein” outer shell that is proteins & lipids mixed together to make it more water soluble in blood.
Shell that carries lipids through blood
What are the 4 types of lipoproteins?
- Chylomicron (Highest fat, lowest protein)
-Formed in GI; final in liver
-carry triglycerides & cholesterol - VLDL
-secreted by liver; travel to peripheries
-converts to LDL - LDL - Primary circulating in body
-produced from liver; excess in arteries
-“Bad cholesterol” associated w/ CAD - HDL (lowest fat, highest protein)
-produced in liver
-“Good cholesterol”
-scavenger of cholesterol from cells & other lipoproteins & takes them back to liver to be excreted in bile
-Decreased levels associated w/ atherosclerosis
What is the good cholesterol and why?
HDL - high density lipoprotein
Scavenges bad cholesterol & takes it back to the liver to be excreted in bile
Describe the difference between triglycerides and cholesterol
Cholesterol: Sterol molecule and important for a number of precursor molecules needed within cell
triglycerides: Majority of neutral fats and consists of glycerol esters combined with fatty acids
What is the lab test associated with cholesterol? what are the most important values on there?
Lipid profile
Total cholesterol & LDL/HDL ratio
What is the normal LDL/HDL cholesterol ratio? If this ratio is increased, what does this mean? Give an example.
Ratio = LDL / HDL
Normal = 120 / 40
Approxiamtely = 3
If this is increased that means the risk of developing CVD from cholesterol is increased
Ex) Ratio = 240/40 –> 6
Since normal ratio is 3; 6 is 2x more than 3; you are 2x more likely to CVD related to cholesterol
What are normal cholesterol levels?
Total cholesterol < 200
LDL <130
HDL > 40
T/F: if total cholesterol is >200 and LDL is normal, but HDL is high, you most likely won’t get put on a -statin
T
What is Familial hypercholesterolemia?
Genetic disorder that causes increase in LDL
More likely to develop CAD d/t problem regulating LDL
have hyperlipoproteinemias
What are some secondary causes of dyslipidemia?
DM
Estrogen use
Acromegaly (excess growth hormone produced by pituitary gland)
What are diet considerations when trying to lower cholesterol?
- only eat 20% of calories from fat
- eat more complex cars & fiber
-lose weight
-eat more omega-3 fatty acids
Besides high cholesterol, what is another reason to be put on a statin?
Previous MI
Heart disease
Where do most dyslipidemia drugs target?
heptatocytes in the liver
Drugs: Statins
-Statin
Class: Statins
MOA: Block HMG-CoA reductase enzyme -> reduces cholesterol synthesis in the liver
-Reduce LDL (which causes increase in LDL-R) & trigylcerides
-slight increase in HDL
Take with food - increases absorption
Toxicity: elevated liver enzymes
-Muscle pain/weakness that may be severe if so, switch them off this medication
-elevated CK
Compare a statin & HMG-CoA reductase enzyme
They have similar structures
Statins work as a competitive inhibitor. They binds to HMG–CoA and which prevents HMG-CoA reductase from binding and prevents conversion to cholesterol.
Why do LDL receptors increase when LDL decreases?
To scavenge LDL from the blood
When does cholesterol synthesis happen?
At night
T/F: Its okay to give statins to pregnant women, breastfeeding women, or children
FALSE
IT IS NOT OKAY!!!!!!
THEY NEED THEIR CHOLESTEROL
YOU DO NOT BLOCK CHOLESTEROL IN ANY OF THESE POPULATIONS OF PEOPLE
Do not give them any medication that blocks their cholesterol even outside of statins
Drugs: Niacin
Vitamin B3
Class: Niacin
MOA: Blocks movement of cholesterol into VLDL lipoproteins
Decreases VLDL/LDL
Increases HDL
Incorporated into NAD (energy producing pathway)
Megadose of 2-6 GRAMS needed
Toxicity: #1 effect = cutaneous vasodilation which is flushing in the face.
- elevated liver enzymes
-pruritis
-GI discomfort
What is the 1st lipoprotein that comes from the liver? what is it converted to?
VLDL
LDL
Drugs: Gemfibrozil
-fib-
Class: Fibrates
MOA: Increase lipolysis in the liver through PPAR which decreases lipid production
decreases VLDL & LDL
Toxicity: GI
Drugs: Bile acid binding resins
Class: Bile acid binding resins
MOA: Large cation exchange resins surround food & prevent binding to cell membrane in intestine
- lipids not absorbed/prevent reabsorption
Need to be used in conjunction
May increase VLDL (not getting in diet so liver wants to produce more)
Granular preparation in liquid
Must be taken with meals
Toxicity: GI
Maybe not give this med to patients who are already have an issue with malabsorption or malnutrition
DO NOT TAKE THIS WITH OTHER MEDS BC OTHER MEDS WONT BE ABSORBED
Drugs: Ezetimibe (Zetia)
Class: Inhibitor of intestinal sterol absorption
MOA: inhibits NPC1L1 transporter and prevents the uptake of cholesterol in the gut
Reduces LDL
Toxicity: Liver issues? arterial wall thickening?
What is the cholesterol transporter in the gut called?
NPC1L1
The ______ are cells line the GI tract
enterocytes
Drugs: Evolocumab
Class: Monoclonal anitbody
PCSK9 inhibitor
MOA: Bind to PCSK9 (which inhibit LDL-R) to allow more LDL-R to allow statins to work better
Must be taken in conjuction with statins
LDL lowered to <25 mg/dL
What is hypocholesterolemia associated with?
Cancer
Hemorrhagic stroke
depression
anxiety
preterm birth and low birthweight
