Dyslipidemia (Wendt & Gonzalvo) Flashcards
Apoplipoproteins Role:
ApoA-1
(structural in HDL)
mediates reverse of cholesterol transport
Apoplipoproteins Role:
ApoB-100
structural in VLDL; IDL; LDL; LDL receptor ligand made in liver
Apoplipoproteins Role:
ApoB-48
produced in intestines/structural in chylomicrons
Apoplipoproteins Role:
ApoE
does reverse cholesterol transport with HDL;
Apoplipoproteins Role:
ApoCIII
inhibits LPL and interferes w/ ApoB and ApoE binding to hepatic receptors
ApoB48 will be found on ______
chylomicrons
ApoB-100 will be found on _______
VLDLs; IDLs; LDLs
Ratio of what two things is important for assessing CVD risk (per Wendt lecture)
ratio of Total Cholesterol: HDL cholesterol
Diseases assoc. with Hypertriglyceridemia
Pancreatitis
Xanthomas
Increased risk in CHD
Diseases assoc. w/ Hypoerlipoproteinemia
Atherosclerosis
Premature CAD
Neurologic disease- stroke
What TC:HDL ratio is considered increase risk for CVD
> 4.5
There are ____ receptors on endothelial cells - helps lead to atherosclerosis
LDL
Atheroslerosis
LDL in blood gets into ________ which leads to ______ cells then _______
monocytes; foam cells; fatty streak
How Statins Increase LDL Receptors:
Statins cause there to be less ______ in the blood, therefore the _______ are no stuck anymore and can go _______
cholesterol(sterols); proteases (arent stuck anymore); go cleave transcription factors (that will increase LDL receptor transcription)
which statins should be taken in the evening with meals (for absorption)
Simvastatin and Lovastatin
which statins have CYP3A4 metabolism?
Simvastatin; Lovastatin; Atorvastatin
which statin does not have metabolism via CYP enzyme? and how is it metabolized?
pravastatin; sulfation!
what is Zetia’s MOA?
inhibits NPC1L1 – aka will inhibit intestinal absorption of cholesterol from dietary sources and reabsorption of cholesterol in the bile
what drugs inhibit Apo B lipoprotein synthesis
Lomitapide; Mipomersen
what is the fibrate class of drugs’ MOA?
fibrate binds to PPAR-alpha and aso RXR; all of that binds to PPRE with drives LPL expression! it also increase expression of ApoA1 (aka HDL expression)
what is PSCK9s normal job (not talking about drugs)
PCSK9 = promotes degradation of LDL receptors in the liver
MOA for Omega 3 fatty acids
inhibits synthesis of TGs in liver –bc it is a poor substrate for enzymes that make TGs
Niacin will reduce TGs by:
- increase ______ activity to increase _____ clearance
- decrease _______ production
- strongly increase _______ levels
increase Lipase; increase VLDL clearance
decrease VLDL production
increase HDL levels
Niacin works in ______ tissue and which organ?
adipose; liver
Niacin:
works in adipose tissue by decreasing Fatty Acid transport to liver by _________
inhibiting TG lipolysis by hormone sensitive lipase
Niacin:
works in liver by inhibiting ________ and ______
fatty acid synthesis and esterification
what things can reduce HDL
- smoking
- T2DM
- Obesity
- Malnutrition
- Drugs (anabolic steroids and Beta blockers)
what things can lead to elevated LDL
- hypothyroidism
- nephrotic syndrome
- cholestasis
- anorexia nervosa
- Drugs: Thiazides; cyclosporine; tegretol
steps for Pathogenesis of Atherosclerosis:
- endothelial injury
- inflamm. response
- macrophage infiltraiton
- platelet adhesion
- smooth muscle proliferation
- extracellular muscle accumulation
Common signs for dyslipidemia
- pancreatitis
- eruptive xanthomas
- peripheral polyneuropathy
- increased BP
- Waise Size
(> 40 in in men; > 35 in women) - BMI > 30 kg/m^2)
Common Sx of Dyslipidemia
- chest pain/palpitations
- Sweating/anxiety/SOB
- Loss of consciousness
- Difficulty w/ speech or movement
- abdominal pain
- sudden death
how to calculate LDL
LDL = TC - HDL - TG/5
what lab parameters are used for dyslipidemia
HDL; TC; TG; LDL
what things are needed for BOTH Framingham and Pooled cohort eqns
- gender
- age
- HDL
- Systolic BP
- Tx for HTN
- Smoking
- Total Cholesterol
what things are needed for pooled cohort eqn and NOT framingham
race; diabetes
Statins and Muscle Injury:
if CK is ______ times the upper limit - stop the statin!
10
why is grapefruit juice a possible issue with statins
grapefruit juice is a CYP3A4 inhibitor - will elevate statin levels — higher risk of muscle injury
when to monitor Statins?
baseline
4 - 12 weeks after starting statin initiation
every 3 - 12 months as clinically indicated
ADEs of Bile acid resins
impaired absorption of fat soluble vitmains
hypernatremia
hyperchloremia
GI obstruction
Niacin will
_____ LFTs
and lead to _____uricemia and ______glycemia
_____ statin levels
increase;
hyper; hyper;
increase
Fibrates will increase the levels of what drugs
- statins
- zetia
- sulfonylureas
- warfarin
which lipid drug is an oligonucleotide inhibitor of ApoB-100 synthesis
Mipomerson
which lipid drug is an inhibitor of a triglyceride transfer protein
lomitapide
what are guidelines used for Lipid therapy
and in the order they were implemented
NECP ACC/AHA NLA ACC - non statin NLA - PCSK9
what are 4 statin benefit groups
- Clinical ASCVD
- LDL > 190
- Diabetes and ages 40 - 75
- ASCVD risk > 7.5% and ages 40 - 75
if someone has clinical ASCVD what type of statin should they be on
if > 75 yo - moderate intensity
if < 75 yo - high intensity
if someone is b/w ages 40 - 75 and has diabetes what type of statin should they be on
if ASCVD risk > 7.5% - high intensity
if ASCVD risk < 7.5% - moderate intensity
if someone has an LDL > 190 and has diabetes what type of statin should they be on
high intensity
what are the high intensity statins
ator. 40 - 80
rosuv 20 - 40
what are the major risk factors for ASCVD (for NLA statin)
- Age: M > 45; W > 55
- HDL: M < 40; F: 50
- HTN?
- Smoker?
- FH of early CHD: first degree relative —- M: < 55; F < 65
goals for NON- HDL and LDL if put into NLA VERY high risk group
NON-HDL < 100
LDL < 70
goals for NON- HDL and LDL if put into NLA low, mod, or high risk group
NON-HDL < 130
LDL < 100
NLA Guidelines:
Who is low risk
0 - 1 major risk factor
NLA Guidelines:
who is mod risk
2 major risk factors + ASCVD risk b/w 5 - 15%
NLA Guidelines:
who is very high risk
Clinical ASCVD
OR
DM with 2+ Risk Factors
NLA Guidelines:
who is high risk
- CKD 3B/4
- LDL > 190
- DM w/ 0 - 1 risk factors
- 3+ risk factors
- 2 risk factors + (pooled: > 15%; framingham >10%)
