Dyslipidemia Flashcards
What is the leading cause of death in the US?
Atherosclerosis (specifically CAD)
What is the basic process by which plaque forms?
- LDL brings cholesterol into the cell
- LDL is oxidized by reactive oxygen species (ROS)
- oLDL (oxidized LDL) is taken up by a macrophage & cholesterol is absorbed into macrophage forming a “foam cell”.
- Foam cell bursting & the resulting deposition of cholesterol forms the basis for plaque formation.
What are the two main lipids associated with CAD?
- Cholesterol
- Triglycerides
What lipid forms fat tissue/buildup & is the basis for metabolic syndrome?
Triglycerides
Blood levels of cholesterol are considered high at _______ mg/dL.
200
How long would it take to lower cholesterol, without a statin, through diet & lifestyle changes alone?
3-5 years
What is the synthesis pathway for cholesterol?
Acetyl-CoA → HMG-CoA → HMG CoA-reductase → Mevalonate → Cholesterol
What is the rate-limiting step in the cholesterol synthesis pathway?
Where do statin’s inhibit cholesterol formation?
- Mevalonate
- HMG-CoA reductase
What is the largest high-fat/low-protein lipoprotein?
Where are these made?
What do they carry?
Where are they degraded? What should be known about their degraded products?
- Chylomicrons
- GI tract.
- Carry triglycerides & cholesterol
- Degraded by cells, then liver; remnants are pro-atherogenic.
VLDLs are secreted by what?
What are they converted to? How?
- Liver
- VLDLs are converted to IDLs & LDLs via the endogenous pathway.
An excess of LDLs results in an excess of cholesterol in the ________.
How do HDLs differ from this?
- Arteries
- HDLs “scavenge” cholesterol from the arteries. ↓ HDLs are associated with atherosclerosis.
How are VLDL’s calculated?
How about LDL’s?
VLDL = Triglycerides/5
LDL = Total cholesterol - VLDL - HDL
What would a normal LDL/HDL ratio be?
What ratio would half one’s risk of CAD?
What ratio would double ones risk of CAD?
3 to 3.5
1 to 1.5
5 to 6
What two factors can invalidate a measure LDL/HDL ratio?
- Triglycerides greater than 400mg/dL
- Chylomicrons present in sample
What would a normal HDL level be in someone?
around 45 mg/dL
Familial hypercholesterolemia involves increases levels of what?
LDLs
What two conditions, highlighted in lecture, result in hypertriglyceridemia?
- Diabetes Mellitus
- EtOH abuse (↑ NADH)
What three dietary intakes can be used to decrease risk of atherosclerosis? Give the reasoning why for each example.
- ↓ cholesterol
- ↓ fat, alcohol, & excess calories =↓ triglycerides
- ↓ sucrose/fructose = ↓ VLDLs
What other dietary measures can be utilized to help decrease risk of atherosclerosis?
- 20% of calories from fat
- ↑ fiber
- weight reduction
- ↑ intake of Ω-3 fatty acids.
What is the most important hyperlipidemia medication?
What is the primary result of these drugs?
When are they prescribed?
- Statins (HMG-CoA reducase inhibitors)
- ↓ LDL & cholesterol levels
- Prescribed with CAD symptoms regards of lipidemia.
What are the 4 facets of a statin’s mechanism of action?
- ↓ cholesterol synthesis
- ↑ LDL reuptake (scavenged from liver)
- modest ↓ in triglycerides
- small ↑ in HDL
When are statins typically administered? Why?
What is the dosing for pregnant & lactating women.
- With food and/or at bedtime (cholesterol synthesis occurs at night.)
- Not given to pregnant/lactating women.
What are the two adverse outcomes of statin toxicity?
- ↑ liver enzymes (especially if patient is of asian descent)
- ↑ CK & muscle pain or weakness (typically minor but can be major)
How does Niacin (Vitamin B₃) treat dyslipidemia?
Reduction of VLDL secretion from liver = ↓ VLDL/LDL & ↑ HDL.
What does Niacin toxicity cause?
- Cutaneous vasodilation (flushing)
- ↑ liver enzymes
How do Fibrates treat HLD?
↑ lipolysis in the liver
How do Bile-acid binding resins work?
What is the prototypical drug of this class?
When are they given?
What can occur with other orally administered drugs if given with these?
- BABRs bind to bile acids & prevent reabsorption of food.
- Colesevalam HCl
- Given with meals.
- Decreased absorption of other PO drugs.
How does Ezetimibe work?
Inhibition of sterol absorption in the intestine by blocking cholesterol transport.
What is the one-sentence MOA of PCSK9 Inhibitors?
Prevention of LDL receptor from being recycled by inhibiting the PCSK9 molecule from tagging the receptor for destruction.
What molecule targets an LDL receptor for destruction instead of recycling?
PCSK9
PCSK9 Inhibitors with statins lower LDL levels by ______.
65%
Gemfibrozil (lopid)
decreases VLDL
modest decrease in LDL
toxicity - rate (GI upset)
increases lipolysis in liver (PPAR)
Evolocumab (Repatha)
LOWERED LDL 65%
mild allergy side effect (nasopharyngitis)
monoclonal antibodies - binds PCSK9, inhibit
injection 1x/2 weeks
