HyperLip pathopharm (325E1) Flashcards
cholesterol is a building block for what
-estrogen and testosterone
-Vit D
-Cortisol
-Bile salt
-found in skin to help decrease evaportion of H2O & blocks absorption of water sol molecules
essential part of the lipid bilayer
is cholesterol soluble or insoluble
highly insoluble (does not break down easily)
exogenous vs endogenous cholesterol
-exo: dietary chol, 25%
-endo: body makes (spec liver cells) in response to dietary chol , 75%
what is the pathway in which cholesterol is produced
HMG-CoA reductase
what does liver use saturated fat for
to make more cholesterol so if you have an increased intake of sat fat then your liver will make cholesterol
what receptor pulls cholesterol out of the blood
LDL receptor (negative feed back loop: LDL attaches to receptors -? HMG CoA concerts into chol -> if excess chol then pathway is blocked & the body recognizes this & thinks it needs more so -> more LDL receptors are made to pull out chol)
what lipoprotein (cholesterol) is considered good and has a good source of protein
HDL-C (50% pro)
what lipoproteins (cholesterol) are considered bad
-LDL-C (sticks to artery wall & causes build up)
-VLDL-C (cant measure but high in TAGs & TAGs can be measured)
**correlate with risk of heart disease)
hyperlipidemia
too much cholesterol in the blood
when checking cholesterol levels, what do we want to test
fasted levels ; eating can cause large variation compared to baseline levels
why is screening of hyperlipidemia important
it is a silent disease so people >20y/o should be screened every 5 years, can start younger if at high risk
cholesterol normal range
100-200 (goal <200)
what is the best lab to test for hyperlipidemia
total cholesterol = HDL + LDL + (TAGs/5)
HDL goal values
M: >55 mg/dL
W: >45 mg/dL
optimal >60
LDL goal values
<100 mg/dL
triglycerides goal values
40-150 (goal <150)
LDL to HDL ratio goals
M: <5.0
F: <4.5
if slightly elevated LDL but high HDL, can balance out
familial hypercholesterolemia
caused by a defect in LDL receptors (so cannot pull LDL from blood) in the liver cells so it does not matter what the person eats, they will still have high cholesterol -> hard to treat & worse if inherited from both parents
why might you see a child with heart disease or have a MI
familial hypercholesterolemia
general risks for high cholesterol
-age, family hx (non controllable)
-cigarette smoking, htn, dm, physical inactivity, obesity, poor diet w/ high sat fat (controllable)
why do we care when cholesterol is high
it causes atherosclerosis
what increases you risk for atherosclerosis
elevated LDLs and cholesterol
arteriosclerosis
-a specific type of atherosclerosis
-thickening or hardening of the arterial walls
-most symptomatic
-used interchangeably w/ atherosclerosis
why is arteriosclerosis so concerning
it blocks the arteries which bring oxygenated blood to the tissues
after there is a build up of cholesterol, how does atherosclerotic plaque form
HTN/Hyperglycemia/smoking -> injury from chronic irritation to the endothelium -> plaque begins to form in arteries bc LDL want to pack the damaged areas
what does injury do to permeability
it increases permeability so the cells instead of being tightly packed, they’re more open and anything can get into them LDL vessel into wall
when LDLs vessel into the damaged tissue walls, what process occurs
the inflammatory process begins so macrophages arrive and they try to engulf the lipids which produces foam cells
foam cells
fatty streaks on the vessel wall and they lead to the development of plaque
lipid core
lipid cells + foam cells
when large, prone to rupture
what happens when a lipid core rupture
a clot can form and everything beyond that point will not get oxygen or nutrients unless we get that vessel back open
what minimally invasive test can we run to look for atherosclerosis
look at the inflammation mark CRP it is non specific so we also look at high cholesterol and risk factors to determine likelihood of atherosclerosis
can also use erythrocyte sedimentation rate
what type of plaque are more stable (less likely to rupture)
older plaques because they have more collagen and fibrins in them older does not mean worse
how can people have large artery blockages but not have symptoms
-low physical activity so they do not need a lot of increased blood flow
-if the obstruction is in a small vessel that doesn’t carry much blood so effects go unnoticed
look for fatigue, angina, inability to do activities they used to as main signs
what is atherosclerosis a big risk factor for
CAD, heart attacks, strokes
CAD
plaque build up in the heart leading to insufficient delivery of oxygen to the heart -> ischemic heart disease
atherosclerosis
what do we do for atherosclerosis
lower cholesterol in blood
-decrease LDL
-increase HDL
do this by meds, diet, exercise, wt loss, stop smoking
main drugs for atherosclerosis
HMG-CoA redutase inhibitors “statins”
when to start medications after diet and lifestyle changes do not work
6 months
if we stop HMG CoA reductase, what do we stop
the liver from making endogenous cholesterol
who will not respond to statins
people with familia hypercholesterolemia bc they do not have working LDL receptors
benefits of statins
-prevent nonfatal and fatal cardiac events (stroke & MI)
-reduce risk of disability from non fatal stroke (women have a greater of disability post stroke)
-put pt who have had an event on for prevention
-primary & secondary preventions
who are the four people who benefit from statins
-people who have ASCVD (prior stroke or MI)
-people w/ LDL >/190
-people 40-75yo w/ DM who have LDL between 70-189
-estimated 10 year risk of ASCVD 7.5% or higher
MOA of statins
inhibits HMG-CoA reductase so less cholesterol is produced & then liver makes more LDL receptors which also pull cholesterol out of the blood
also stabilizes plaque & decrease inflammation
can you stop taking statins after your levels normalize
no, it is a life long drug bc it is not a permanent drop in levels
effects of statins
LDLs decrease by 21-63%
HDLs increase by 5-22%
TG decrease by 6-43%
adverse reactions of statins
myopathy (muscle weakness) -> rhabdomyolysis (breakdown of muscle fibers & leads to AK failure)
what should you monitor in someone taking statins
liver and kidney labs
how long does it take to see effect of statins
2 weeks
what statins need to be taken at night
simvastatin and rosuvastatin bc chol is highest at night and these drugs have short half lives
cholesterol absorption inhibitor MOA
blocks absorption of choleseterol
what is the first line drug for atherosclerosis
statins
why don’t cholesterol absorption inhibitors work as well as statins
they affect dietary cholesterol which only makes up 25%
what do we do before we give anyone cholesterol meds
-fasting lipid panel
-ALT (liver)
-CK (rhabdo)
-consider secondary causes
what drugs cause elevated LDLs
diuretics, cyclosporine, glucocorticoids, amiodarone
what are other drugs used to treat hyperlipidemia
-bile acid sequestrants
-niacin
-fibric acid derivatives (fibrates)
-fish oil
what is the gold standard for hyperlipidemia treatment
statins w/ diet & exercise
