Dyslipidemia (Exam IV) 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%
