Hyperlipidemia

Question 1

Atherosclerotic plaques constrict vessels and lead to

Answer 1

thrombosis, a blood clot occluding a major artery. Causes strokes and heart attacks (myocardial infarction)

Question 2

Plaques build up over time. Arterial damage (possibly hypertension related) leads to

Answer 2

an aggregation of platelets, macrophages filled with oxidized lipids (foam cells), including cholesterol. Ruptures can precipitate immediate clotting and infarction

Question 3

Cholesterol plays an important role in

Answer 3

regulating the lipid microenvironment (fluidity; lipid rafts).

Question 4

Transporting lipids in blood is a problem since blood is _______ and lipids are _________.

Answer 4

aqueous; hydrophobic

Question 5

Most lipid transport in blood is via carriers called

Answer 5

lipoproteins

Question 6

Lipoprotein outer surface

Answer 6

Outer surface is largely a monolayer of triglycerides mixed with an apolipoprotein

Question 7

Lipoprotein inner surface

Answer 7

Inner layers are mixtures of lipids including cholesteryl esters (nonpolar)

Question 8

As density of particles increases, fat (triglyceride) content ______ while protein content _______.

Answer 8

declines; increases. Size also changes, with smaller particles being more dense

Question 9

Fats from GI are packaged into large ________ particles. These distribute to tissues and have fatty acids removed by lipoprotein lipase via interaction with apolipoprotein C. ________ go to liver.

Answer 9

chylomicron; Remnants

Question 10

VLDL remnants (IDLs) are depleted of ________ and picked up by liver, or converted into ____________.

Answer 10

triglycerides; LDL particles

Question 11

LDL have primarily Apo

Answer 11

B-100

Question 12

What percent of cholesterol is reabsorbed and transported back to the liver?

Answer 12

90%

Question 13

If fasting, _______ and ________ are approximately 0

Answer 13

IDL and Chylos

Question 14

TC=

Answer 14

LDL+HDL+VLDL+IDL+CHYLOS

Question 15

VLDL ~

Answer 15

Trig/5 if Trig < 450

Question 16

Primary goal of drug therapy

Answer 16

lower LDL-cholesterol

Question 17

Secondary goal of drug therapy

Answer 17

is increase HDL or lower triglycerides

Question 18

Statins

Answer 18

Remarkably effective. Cause up to 60% reductions in LDL cholesterol, 10% increase HDL, slight declines in triglycerides. Also reduce C-reactive protein.

Question 19

Ezetimibe

Answer 19

Cholesterol absorption inhibitor.

Question 20

statins MOA

Answer 20

Block HMG-coA reductase, the rate limiting enzyme in cholesterol synthesis in liver. The decrease in liver intracellular cholesterol leads to increased LDL-R expression and uptake of LDL cholesterol from the circulation

Question 21

statins adverse effects

Answer 21

• Headache – Myalgia – Fatigue
  
  • GI intolerance – Flu-like symptoms
    increases in liver enzymes, liver myopathy,
    -interacts with grapefruit juice

Question 22

30% reduction in cardiovascular disease risk with

Answer 22

statin use in high risk populations

Question 23

Fibric Acid derivatives MOA

Answer 23

Activate PPAR-alpha leading to increased lipoprotein lipase and reduced circulating triglycerides

Question 24

Fibric Acid derivatives drugs

Answer 24

Gemfibrozil, fenofibrate

Question 25

Bile acid sequestrants MOA

Answer 25

Binds bile acids in gut increasing excretion. Leads liver to increase LDL-R to obtain more cholesterol for synthesizing increased amounts of bile acids

Question 26

Bile acid sequestrants drugs

Answer 26

Cholestyramine, colestipol, colesevelam

Question 27

Niacin MOA

Answer 27

Reduces VLDL production by liver and Apo-B100 thereby reducing LDL in circulation

Question 28

Cholesterol Absorption Inhibitors

Answer 28

Ezetimibe

Question 29

Lomitapide treats

Answer 29

Familial Hypercholestrolemia due to homozygous loss of LDL-R

Question 30

Lomitapide MOA

Answer 30

Blocks microsomal triglyceride transfer protein. reduces LDL

Question 31

Absorption inhibitors MOA

Answer 31

Block uptake from GI tract to liver. Increase liver LDL receptors. Reduces circulating LDL